Effect of low doses of angiotensin II perfusion on the hypotensive action of captopril in anaesthetized normotensive and spontaneously hypertensive rats

The effect of intravenous (i.v.) captopril on mean arterial blood pressure (MABP) of anaesthetized normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats perfused i.v. with two doses of angiotensin II (ANG II; 2.9 and 5.8 pmol/kg per min) was studied to determine the role of the suppression of plasma ANG II in the hypotensive action of captopril. The reduction of MABP by captopril was attenuated in WKY and abolished in SHR by the highest dose of ANG II; it was unchanged in WKY and attenuated in SHR by the lowest dose of ANG II. The suppression of plasma ANG II thus explains a minor part of the acute reduction of MABP by captopril in WKY and a major part of this action in SHR. Plasma ANG II contributes to the maintenance of high blood pressure in SHR.     

Angiotensin II modulates conducted vasoconstriction to norepinephrine and local electrical stimulation in rat mesenteric arterioles

OBJECTIVE: Localized application of a vasoconstricting agent onto the wall of an arteriole results not only in a local constriction of the vessel, but also in a conducted vasoconstriction which is detectable more than a millimeter upstream and downstream from the application site. We investigated the effect of intravenous infusion of angiotensin II (ANG II), losartan or methoxamine on conducted vasoconstriction to local application of norepinephrine (NE) or local electrical stimulation onto the surface of rat mesenteric arterioles in vivo. METHODS: In anesthetized male Wistar rats (n = 43) NE (0.1 mM) or a local depolarizing current was continuously applied onto mesenteric arterioles using micropipettes. Local and conducted vasoconstriction was measured using videomicroscopy. Conducted responses were measured 200-1000 microns upstream from the application site. RESULTS: Systemic infusion of ANG II (4 ng/min) raised mean arterial blood pressure by 6 +/- 2 mm Hg and increased the conducted but not the local vasoconstrictor response to NE (P < 0.02). Infusion of the alpha 1-agonist methoxamine raised blood pressure to the same extent, but did not change conducted vasoconstriction significantly. Blockade of endogenous ANG II by infusion of the AT1-receptor blocker losartan decreased conducted vasoconstriction to NE (P < 0.03). In parallel with the findings using NE, ANG II increased (P < 0.05) and losartan decreased (P < 0.01) conducted vasoconstriction when local electrical stimulation was used to initiate the conducted vascular response. CONCLUSION: The findings suggest that conducted vasoconstriction to NE and local electrical stimulation in rat mesenteric arterioles are modulated by ANG II, an increase in the plasma levels of ANG II increasing conducted vasoconstriction.     

The mechanism of action of angiotensin II in the rat snake, Ptyas korros

The hindquarter of the rat snake, Ptyas korros, was isolated for perfusion study in order to investigate the mechanism of action of angiotensin (ANG) II. Both ANG II and norepinephrine (NE) produced concentration-dependent increases in perfusion pressure. [Sar1, Ile8] ANG II significantly attenuated the response to ANG II but not that of NE. Phentolamine significantly reduced the responses to both ANG II and NE, with much greater inhibition on NE than ANG II. These findings suggest the presence of ANG II receptors and alpha-adrenergic receptors in the hindquarter. Since tyramine did not exert any increase in perfusion pressure, the release of ANG II-stimulated catecholamines was probably not involved in the increase in perfusion pressure to ANG II in the present preparation. The partial attenuation of the response to ANG II by phentolamine, therefore, suggests that ANG II may act directly on both specific ANG II receptors and alpha-adrenergic receptors.     

Studies on the Mechanism of the Enhancement of the Antihypertensive Activity of Captopril by A Diuretic in Spontaneously Hypertensive Rats

Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.     

Hormone replacement therapy increases plasma level of angiotensin II in postmenopausal hypertensive women

The renin-angiotensin-aldosterone system plays a major role in the pathogenesis of hypertension by enhancing the production or the activity of angiotensin II (ANG II). We evaluated the effects of hormone replacement therapy (HRT) on the renin-angiotensin-aldosterone system and on bradykinin in postmenopausal women (PMW) who were hypertensive or normotensive. Subjects included 28 PMW whose elevated blood pressure (BP) was well controlled on antihypertensive agents excluding diuretics, angiotensin-converting enzyme (ACE) inhibitors, and ANG II receptor antagonists. As controls, we evaluated 16 normotensive PMW. All subjects received oral HRT daily for 6 months. The plasma levels of angiotensin I (ANG I), ANG II, and bradykinin as well as plasma renin activity (PRA) showed a significant increase in HRT in the hypertensive group, but not in the normotensive group. The serum ACE activity showed a significant decrease in both groups, but the plasma level of aldosterone was unchanged. Despite the decrease in serum ACE activity, there was an increase in the plasma ANG II level. Hormone replacement therapy increased the level of ANG II in the hypertensive women, but their BP was unaffected. The increase in plasma bradykinin level may maintain homeostasis in the presence of an increase in plasma ANG II, which is a risk factor for cardiovascular disease. Hormone replacement therapy was associated with a decrease in serum ACE and an increase in plasma bradykinin in hypertensive PMW. Accordingly, the protective effect of HRT against cardiovascular disease in PMW can be provided by a decrease in ACE activity and an increase in bradykinin.     

Alpha- and beta-adrenergic mechanisms mediate blood pressure control by norepinephrine and angiotensin in ducks

Adrenergic mechanisms for the pressor actions of blood-borne L-norepinephrine (NE) and fowl angiotensin II (ANG II) were studied in barbiturate-anesthetized adult ducks (Anas platyrhynchos). NE (1.5-6.0 nmol X kg-1) or ANG II (0.4-1.6 nmol X kg-1) injected iv caused dose-dependent increases in mean arterial pressure (Pa) and pulse pressure (Pp) but slowed cardiac frequency (fH); higher doses of ANG II increased Pa, Pp, and fH X beta-Adrenergic blockade by propranolol lowered baseline Pa, completely blocked cardiovascular responses to isoproterenol, augmented the bradycardic effect of NE, and inhibited the stimulation of Pp by ANG II. However, the tachycardiac effect of high-dose ANG II persisted during beta-blockade. alpha-Adrenergic blockade following iv prazosin completely blocked the pressor effect of methoxamine, diminished the pressure response to NE, and decreased Pa sensitivity to ANG II injections. Combined alpha- and beta-adrenergic blockade decreased both the sensitivity and the maximal Pa response to ANG II. We conclude that (i) beta-adrenergic mechanisms predominate in the maintenance of resting Pa, (ii) NE increases Pa principally by alpha-adrenergic action while beta-adrenergic stimulation buffers the consequent bradycardia, and (iii) although the positive chronotropic effect of high doses of ANG II probably is not mediated by catecholamines, low doses of ANG II elevate Pa and Pp by alpha- and beta-adrenergic mechanisms.     

Effects of converting enzyme inhibition and alpha receptor blockade on the angiotensin pressor response in the American alligator.

This study examines the effects of two converting enzyme inhibitors (captopril and enalaprilat) and two alpha-adrenergic receptor antagonists (phentolamine and phenoxybenzamine) on the pressor response produced by exogenous angiotensin I ([Asp1, Val5, Ser9] ANG I, fowl) and [Val5] angiotensin II (ANG II) in the American alligator (Alligator mississippiensis). Bolus administration of ANG I at 0.1, 0.5, and 1.0 micrograms/kg; ANG II at 0.05, 0.1, and 0.5 micrograms/kg; or norepinephrine (NE) at 2 micrograms/kg elicited dose-dependent increases in arterial blood pressure. Captopril (0.5 mg/kg/hr) and enalaprilat (300 micrograms/kg/hr) significantly reduced the response to ANG I, but not ANG II or NE. Both phenoxybenzamine (0.25 mg/kg/min) and phentolamine (1 mg/kg/hr) effectively blocked the NE pressor response (84 and 88%, respectively) and attenuated (42-80%) the pressor effects of ANG I and ANG II. These results support previous work suggesting the alligator may possess a renin-angiotensin system with characteristics similar to those found in mammals and other vertebrates. In addition, the pressor response to exogenously administered ANG I and ANG II was attenuated by alpha adrenergic receptor blockade and thus may be due, in part, to secondary catecholamine release.     

Effect of sodium balance and calcium channel blocking drugs on blood pressure responses

To study the role of calcium movements in mediating the effects of sodium chloride on the response of blood pressure to angiotensin II (ANG II), we infused ANG II before and after giving calcium channel blocking drugs (nifedipine and diltiazem) and calcium infusions to normal subjects during high and low sodium intakes. ANG II was also in nine patients with essential hypertension eating a low sodium diet. In preliminary studies, the effects of nifedipine, 20 mg p.o., on blood pressure and plasma renin activity were determined. Sensitivity to infused ANG II was calculated as the slope of the linear regression of the increase in diastolic blood pressure (DBP) expressed as a function of the ANG II infusion rate (mm Hg/ng ANG II/kg/min). During intake of a high sodium diet (Na, 200 mEq/day) both drugs significantly (p less than 0.05) reduced ANG II sensitivity, while on a low sodium diet (10 mEq Na), neither drug reduced ANG II sensitivity. There was a significant (p less than 0.001) inverse correlation between the initial ANG II-DBP sensitivity and the change in sensitivity induced by the calcium channel blocking drugs in normal subjects (r = -0.78) and in hypertensive patients (r = -0.70). Five hypertensive patients had greater than normal ANG II-DBP sensitivity that was significantly (p less than 0.05) reduced by nifedipine. Calcium infusion did not affect the ANG II-DBP sensitivity on either diet. The results suggest that in normal subjects increased DBP responses to ANG II, induced by an increase in sodium intake, are partially mediated by increased extracellular to intracellular calcium movements, since they are blocked by the structurally different calcium channel blocking drugs nifedipine and diltiazem. In hypertensive patients on a low sodium diet, increased DBP responses to ANG II infusion were blocked by nifedipine, indicating they are at least partly mediated by increased extracellular to intracellular calcium flux.     

The effects of verapamil SR and bisoprolol on reducing the sympathetic nervous system's activity.

To assess the response of the sympathetic nervous system (SNS) to the handgrip test in essential hypertensive patients and to evaluate the effects of verapamil SR and bisoprolol on the reduction of the SNS's activity. Seventy eight essential hypertensive patients (50 receiving verapamil SR treatment and 28 receiving bisoprolol treatment) took the handgrip test while the SBP, DBP, and HR were measured on three occasions during the test (before test, 3 min after the patients squeezed the handgrip, and 2 min after the handgrip was released). Before and after the patients received Verapamil SR or Bisoprolol treatment, the plasma concentrations of epinephrine(E), norepinephrine (NE), angiotensin-II (AII), aldosterone (ALD), endothelin-1 (ET-1) and renin activity (RA) were measured post-test. 1) In about 70% of the essential hypertensive patients, SNS activity was above normal. Their HR and BP exceeded 20% when responding to stress. 2) In these patients, the baseline plasma concentrations of E, NE, AII, ET-1, ALD, and RA were higher than those whose SNS's activity was normal. 3) After 6 weeks of treatment, all the patients' BPs decreased remarkably. Verapamil SR could reduce the plasma concentrations of NE, AII, and ET-1 and increase RA. Bisoprolol could reduce E and RA. These two antihypertension drugs can both decrease BP and reduce the activity of SNS through different mechanisms.     

Chronic angiotensin II infusion decreases renal norepinephrine overflow in conscious dogs

Sympathetic nerve activity and in particular renal sympathetic nerve activity were monitored in six conscious dogs subjected to 6 days of intravenous angiotensin (ANG II) infusion (20 ng/kg/min). This was accomplished by measurement of both arterial and renal venous plasma catecholamine concentration. During the initial 4 hours of ANG II infusion, mean arterial pressure (MAP) increased 35 +/- 8 mm Hg from a control value of 101 +/- 4 mm Hg. Although there were no significant changes in arterial plasma norepinephrine (NE) concentration at this time (control = 148 +/- 40 pg/ml), arterial plasma epinephrine (E) concentration increased threefold (control 42 +/- 15 pg/ml). After 24 hours of ANG II infusion, MAP remained elevated (132 +/- 5 mm Hg), but plasma E concentration returned to control levels. From Days 2 through 6 of ANG II infusion, MAP was elevated approximately 40 mm Hg, but there were no chronic increases in either arterial plasma E or NE concentrations. In contrast to arterial plasma catecholamine concentration, renal vein plasma NE concentration (control = 216 +/- 27 pg/ml) actually decreased during both the acute (122 +/- 12 pg/ml) and chronic (103 +/- 26 pg/ml) phases of ANG II infusion. Moreover, renal NE overflow (renal venous plasma NE concentration-arterial plasma NE concentration X effective renal plasma flow), an index of renal sympathetic nerve activity, was depressed during the chronic phase of ANG II hypertension. These results, therefore, do not support the contention that the sympathetic nervous system mediates the hypertension produced by elevated plasma levels of ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives

BACKGROUND: Individuals differ in their blood pressure (BP) response to changes in dietary sodium (Na+) intake. It is possible that differences in BP responses to dietary Na+ are influenced by genes. METHODS: A total of 35 older (62.9 +/- 1.2 years) hypertensive subjects had their mean arterial blood pressure (MABP) determined after 8 days of low (20 mmol/day) and high (200 mmol/day) Na+ intake. The insertion/ deletion polymorphism of the angiotensin converting enzyme (ACE) gene was genotyped with standard polymerase chain reaction methods. RESULTS: Of the 35 subjects, 24 were classified as sodium-sensitive (> or = 5 mm Hg increase in MABP in response to the increase in dietary Na+) and 11 were classified as sodium-resistant (<5 mm Hg increase in MABP). Those homozygous for the insertion allele of the ACE gene (insertion/insertion [II]; n = 8) had lower (P = .04) MABP responses to the increase in dietary Na+ (0 +/- 3 mm Hg) compared to heterozygotes (insertion/deletion [ID]; n = 20) (9 +/- 2 mm Hg; P = .0001) and those homozygous for the deletion allele (deletion/deletion [DD]; n = 7) (9 +/- 3 mm Hg; P = .05). The prevalence of sodium sensitivity was higher (P = .0083) in DD (71%) and ID (83%) compared to II (25%) genotype groups. CONCLUSIONS: Based on these data in older hypertensive individuals, we conclude that the ACE gene ID and DD genotypes are associated with an increase in BP during a high Na+ diet, which is consistent with the phenotypic characteristic of sodium sensitivity.     

Renin–Angiotensin System Modulates Neurotransmitters in the Paraventricular Nucleus and Contributes to Angiotensin II-Induced Hypertensive Response

Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin–angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN.     

Role of angiotensin II in the hormonal, renal, and electrolyte response to sodium restriction

Adrenal responses to angiotensin II (ANG II) are enhanced with restriction of sodium intake. To determine whether increased circulating ANG II levels are responsible for the enhanced responsiveness, the adrenal and blood pressure responses to ANG II in human subjects were assessed four times: in balance on a high and a low salt diet and before and after the administration of a converting enzyme inhibitor (enalapril). Before enalapril administration, sodium restriction significantly increased (p less than 0.02) plasma renin activity, ANG II, and aldosterone levels; the aldosterone response to ANG II was enhanced twofold (p less than 0.01); and the blood pressure response to ANG II infusion was reduced significantly (p less than 0.05). Despite a fixed and low plasma ANG II concentration when enalapril was employed, the adrenal response to ANG II on the low salt diet was enhanced to the same degree as that observed before administration of the converting enzyme inhibitor. Conversely, enalapril substantially altered the blood pressure response to ANG II with sodium restriction, completely preventing the reduction in responsiveness. If the subjects were first given enalapril and then sodium intake was restricted, ANG II levels did not change significantly but renal excretion of both sodium and potassium was substantially modified. The rate at which renal excretion of sodium fell to match intake was retarded strikingly (p less than 0.001); conversely, renal retention of potassium increased significantly (p less than 0.03) as low salt balance was attained. Possibly because of the potassium retention, aldosterone levels rose, but significantly less than when enalapril was absent.     

Hormonal profile and participation of nitric oxide in salt-sensitive and salt-resistant essential arterial hypertension

Recent studies have shown that cardiovascular events and end-organ damage occur more frequently in patients with salt-sensitive essential hypertension (SH) than in salt-resistant essential hypertension (RH). Nitric oxide (NO) plays an important role in regulating the pressure-natriuresis relationship. Therefore impaired NO synthesis may produce or aggravate salt-sensitive hypertension. This study was conducted to determine the hormonal levels and nitric oxide metabolites in hypertensive patients. 25 patients underwent salt sensitivity testing. 24 h ambulatory blood pressure was recorded after a 5-day period on low salt diet (20 mEq/d) and after a 5-day period on a high salt diet (200 mEq/d). Subjects showing > or = 10 mmHg increase in mean BP when changing from low to high dietary salt intake were classified as salt sensitive and as salt resistant when the BP changes were < 10 mmHg. Based on BP recordings 13 patients were characterised as white coat hypertension (WC), 13 patients as salt resistant (SR) and 12 as salt sensitive (SS). A significative relationship was seen between plasma glucose-insulin concentration and body mass index. The ventricular mass index was similar in SS and SR patients. The plasma uric acid, triglicerides and PAI-I were elevated in SS compared with SR, and control group (C). During low sodium intake, plasma renin and aldosterone were decreased in SS compared with SR, and C. No differences in plasma catecholamines or their changes with intake sodium modifications were seen among the patients. During high sodium intake urinary NO excretion increased in SR (38 +/- 9 vs 18 +/- 2 mg/g creat), and C (24 +/- 2 vs 16 +/- 3 mg/g creat) (p < 0.01) but not in SS patients (21 +/- 3 vs 26 +/- 4 mg/g creat). The NO excretion changes showed negative correlation with BP changes (r = 0.49, p < 0.01). During low sodium intake, SR and SS patients showed a normal nocturnal decrease of BP (dippers). During high sodium intake SS patients became non-dippers. Our results showed that patients with salt sensitive hypertension displayed a suppressed renin-aldosterone system, an attenuated nocturnal decline in blood pressure on high-salt diet and an impairment of endothelial function. The relationship between urinary nitrate excretion and arterial pressure suggest that the salt sensitivity of arterial pressure may be related bo blunted generation of endogenous nitric oxide.     

Cardiovascular responses to neurohormones in conscious chickens and ducks

Cardiovascular responses (cardiac frequency, fH; mean arterial pressure, Pa; ischiatic arterial blood flow; Qi; ischiatic vascular resistance, Ri) to 1-norepinephrine (NE), acetylcholine (ACH), [Asp1, Val5]-angiotensin II (ANG II), and arginine vasotocin (AVT) were studied in conscious chickens (Gallus gallus) and Pekin ducks (Anas platyrhynchos). Age-dependent changes, in the cardiovascular variables and the responses to the native avian neurohormones, were also studied in ducks. NE injection caused larger increases in Pa and Ri, and a greater associated fall in fH, in ducks than in chickens. The pressor effect of ANG II was more persistent and developed at a slower rate than the response to NE in both species, although the pressor effect was greater in ducks. Interestingly, ANG II injection caused a tachycardia in these baroreceptor-intact birds. ACH and AVT produced similar rapid falls in Pa and a corresponding tachycardia in both species, although the fH response was greater in ducks. ANG II rapidly increased NE concentration in the arterial plasma of adult ducks, while AVT increased epinephrine (E) concentration. Resting Pa and hematocrit were lower, and fH was higher, in immature ducks. Immature ducks also were less responsive than adults to the cardiovascular actions of NE, ACH, AVT, and ANG II. The results demonstrate differences in the cardiovascular responses to neurohormones in chickens and ducks consistent with a higher level of cardioinhibitory nervous tone and a greater sensitivity to sympathetic stimuli in the aquatic species, which increase during maturation.     

Augmentation of centrally induced alpha-adrenergic vasodepression in spontaneously hypertensive rats

Central alpha-adrenergic mechanisms for cardiovascular regulation were studied by injecting phenylephrine into a recipient rat whose head was isolated from its body by cross perfusion with a donor rat. Blood pressure increases produced in the donor were accompanied by concurrent reduction of blood pressure and sympathetic nerve activity in the recipient rat's body. These effects were abolished when alpha-adrenergic receptors in the perfused head were blocked with phentolamine. By contrast, intracarotid injections of angiotensin increased blood pressure not only in donor but also in recipient rats. The magnitude of phenylephrine-induced vasodepression was significantly greater in spontaneously hypertensive rats (SHR) than in normotensive or DOCA-salt hypertensive ones. Distribution of radioactive microspheres indicated that carotid arterial blood went mainly to the cerebrum, midbrain, and hypothalamus, with almost negligible amounts going to the lower brainstem. Collectively, our results suggest that centrally administered phenylephrine reduces sympathetic vasomotor tone and blood pressure by acting on alpha-adrenergic receptors located in supramedullary brain areas (possibly in the hypothalamus). In SHR, augmented, vasodepressor responsiveness may be due to reduced brain levels of endogenous norepinephrine that could increase the alpha-adrenergic receptors available.     

Alpha-adducin polymorphism, salt sensitivity, nitric oxide excretion, and cardiovascular risk factors in normotensive Hispanics

BACKGROUND: Genetic and environmental factors determine the blood pressure (BP) response to changes in salt intake. Mutations in the alpha-adducin gene may be associated with hypertension and salt-sensitive hypertension. We investigated whether one alpha-adducin polymorphism, the Gly460Trp (G/T) variant, was associated with salt sensitivity, nitric oxide (NO) production; and cardiovascular risk factors in healthy adult normotensive Venezuelans. METHODS AND RESULTS: Subjects (n = 126) were screened for salt sensitivity. The alpha-Adducin polymorphism was tested in salt-sensitive (SS) and salt-resistant (SR) subjects. The G/T and G/G (wild gene) groups had similar BP levels. The G/T subjects had higher LDL-cholesterol (P =.01) and postload glucose AUC (P =.03) than G/G individuals. Genotype frequencies were not associated with BP or salt sensitivity (G/G, 38.1% SS and 61.9% SR vs G/T, 40.7% SS and 59.3% SR). Shifting from high salt to low salt diet produced comparable reductions in systolic BP and diastolic BP in G/T and G/G groups. The G/G and G/T groups excreted similar amounts of sodium on high and low salt diets. The SR subjects carrying the wild or the mutated gene showed no changes in NO metabolite excretion at different levels of salt intake. In SS subjects, the level of NO metabolite excretion was highly dependent on salt intake. A combination of SS and 460Trp mutation enhanced the sodium-dependent modulation of NO production. CONCLUSIONS: In normotensive Venezuelans, the alpha-adducin G/T polymorphism was not associated with BP, salt sensitivity, or with sodium excretion during sodium loading or restriction. G/T was associated with increased LDL-cholesterol and postload glucose levels. In SS, G/T was associated with greater salt-dependent modulation of NO excretion. However, this larger increase in NO excretion was not associated with a larger decrease in BP.     

Contractile response of the isolated dorsal aorta of the snake to angiotensin II and norepinephrine

Vasopressor action is a phylogenetically old function of angiotensin (ANG) II. The action can be ascribed to both direct activation of vascular ANG II receptors and through catecholamine release. In the Rat snake, Ptyas korros, the possible presence of common adrenergic-ANG receptors and their involvement in this action have been proposed. In order to elucidate the vasopressor mechanism of ANG II in the snake, and to test the presence of common adrenergic-ANG receptors, the contractile response of isolated snake dorsal aorta to [Val5]ANG II and norepinephrine (NE) was studied using the cobra, Naja naja and the Rat snake, Ptyas korros. Both ANG II (3 X 10(-11) to 10(-6) M) and NE (10(-8) to 10(-5) M) produced a dose-dependent increase in tension in the aortic strips of Naja, which were more sensitive to ANG II. Phenotolamine, an alpha-adrenergic antagonist, competitively inhibited NE without altering the response to ANG II. [Sar1, Ala8]ANG II inhibited ANG II but did not affect the response to NE. A similar dose-dependent increase in tension in the aortic strips of Ptyas was seen with NE (10(-8) to 10(-5) M) but these strips did not respond to ANG II. These results suggest that functionally separate receptors for ANG II and NE exist in the dorsal aorta of the cobra and that local liberation of catecholamines from the adrenergic nerve terminals do not play a role in the expression of ANG II action. There also exist differences in the nature of ANG II action/receptors among different species of snakes and different vascular beds in the same species.     

Prostaglandin E2, renin and angiotensin II in renovascular hypertension

We studied a group of 12 hypertensive patients (seven men, five women) with unilateral renal arterial stenosis, and evaluated the morphological criteria on renal angiography for the significance of the stenosis and compared them with the prostaglandin-E2 (PGE2), plasma renin activity (PRA), and angiotensin II (ANG II) concentrations in both renal veins. PGE2 and PRA concentrations were significantly higher in renal veins of kidneys with arterial stenosis with patients supine and after sitting up for 15 min, but the ANG II concentration was raised only with the patient sitting. Assuming that a PRA ratio greater than 2 signifies stenosis of haemodynamic importance, correlation to the angiographic classification was seen in 11 of the 12 patients. The PGE2 ratios were better correlated to PRA ratios than to the angiographic findings. ANG II ratios showed an inconstant and variable pattern in relation to the morphological picture. Our results confirm that PGE2 concentrations in renal venous blood increase in parallel to PRA, and may be interpreted as a means of preserving the blood flow in a kidney with arterial stenosis. However, it is unclear whether this increase is the result of dilution factors or of increased net production of PGE2. Determination of PGE2 in renal vein blood apparently gives no additional information about the functional significance of renal arterial stenosis, and PRA determinations remain the best guide in the management of renovascular hypertension.     

Renal response to angiotensin II is blunted in sodium-sensitive normotensive men

BACKGROUND: In hypertension, sodium sensitivity (SS) of blood pressure is associated with renal hemodynamic abnormalities related to increased activity of the renal renin-angiotensin aldosterone system (RAAS). The renal mechanisms of SS in normotensives are unknown. Therefore, we studied whether SS is related to renal hemodynamics and renal responsiveness to angiotensin II (AngII) in young healthy adults. METHODS: Blood pressure (mean arterial pressure (MAP)) and renal function were measured in 34 healthy men after 1-week low-sodium diet (LS; 50 mmol Na(+)/24 h), 1-week high-sodium diet (HS; 200 mmol Na(+)/24h), and 1-week HS-ACEi (enalapril 20 mg/day). The responses of effective renal plasma flow (ERPF; (131)I-Hippuran clearance) to graded infusion of AngII were assessed during each condition. RESULTS: The sodium-induced change in MAP ranged from -7 to +14 mm Hg. SS (a sodium-induced increase in MAP >3 mm Hg) was present in 13 subjects. ERPF was lower in SS subjects during LS and during HS-ACEi. The AngII-induced decrease in ERPF was blunted in SS on LS (-25 +/- 6 vs. -29 +/- 7% in sodium-resistant (SR) subjects, P < 0.05) and on HS (-30 +/- 5 vs. -35 +/- 6%, P < 0.05). The blunting was corrected by angiotensin-converting enzyme inhibitors (ACEi) (-36 +/- 6 vs. -37 +/- 7%). CONCLUSION: SS normotensive subjects have a blunted renal response to exogenous AngII. This is ameliorated by ACEi, supporting a role for inappropriately high intrarenal RAAS activity. As these findings cannot be attributed to subclinical renal hypertensive damage, high intrarenal RAAS activity and altered renal hemodynamics may be primary phenomena underlying SS.