The effect of an acute or chronic treatment with indomethacin on the blood pressure of DOCA/salt and spontaneously hypertensive rats

The intravenous infusion of indomethacin (5 mg/kg/min) for 10 min did not modify the systolic blood pressure of conscious, unrestrained doca/salt hypertensive, spontaneously hypertensive (SH) and normotensive Wistar (NW) rats. However, this dose of indomethacin was sufficient to prevent completely the hypotensive action of arachidonic acid in these animals. The chronic administration of indomethacin to doca/salt treated- and young SH rats was without any effect on the development of hypertension in these animals. These results suggest a limited role for endogenous PGs during the development of these two types of hypertension.     

Hemodynamic effects of amlodipine and benazeprilat in spontaneously hypertensive rats

We wished to assess the hemodynamic effects of administration of the combination of the calcium channel blocking agent amlodipine and the angiotensin-converting enzyme (ACE) inhibitor benazeprilat in conscious spontaneously hypertensive rats (SHR). In SHR previously instrumented for measurement of mean arterial blood pressure (MAP) and heart rate (HR), intravenous (i.v.) injection of amlodipine (0.25-4 mg/kg) produced dose-dependent decreases in blood pressure (BP). Administration of benazeprilat (0.1-10 mg/kg i.v.) decreased arterial MAP, and benazeprilat (10 mg/kg) effectively blocked the effects of exogenously administered angiotensin I (AI). In animals surgically prepared for measurement of BP, HR, and hindquarter, renal, and mesenteric blood flows, administration (i.v.) of the combination of amlodipine (0.5 mg/kg) with benazeprilat (10 mg/kg) evoked a decrease in BP that was greater than that elicited by monotherapy. The tachycardic response observed after administration of the combination was no different from that observed after monotherapy with amlodipine. Simultaneous administration of amlodipine and benazeprilat produced reductions in vascular resistance in the hindquarter, renal and mesenteric beds that were greater than the responses evoked by injection of either agent. The major finding of these studies was that dual therapy with amlodipine and benazeprilat produced an additive hypotensive effect in conscious SHR. Regional vasodilation accompanied the large degree of hypotension evoked by the combination.     

Contribution of humoral systems to the recovery of blood pressure following severe haemorrhage

1. Profound haemorrhage activates a number of pressor mechanisms, including the release of catecholamines, angiotensin II and arginine-vasopressin, which contribute to the subsequent cardiovascular recovery. Using specific single or combined blockade with prazosin, losartan and Manning compound (AVPX), the aim of this study was to evaluate the involvement of the three pressor systems in blood pressure recovery following severe haemorrhage (20 ml kg-1). 2. Haemorrhage of conscious, unrestrained rats resulted in a significant initial decrease in blood pressure of approximately 60 mmHg, and heart rate of approximately 70 bpm. Then, blood pressure tended to return to the control level within 10 min. The total cardiovascular recovery corresponded to increments of 52 +/- 5 mmHg (81% of the acute fall) for systolic blood pressure, and of 92 +/- 22 bpm (124%) for heart rate at 60 min post-bleeding. Significant falls in haematocrit (-10.5 +/- 1.2%, P < 0.01), in plasma concentrations of proteins (-10.3 +/- 0.9 g l-1, P < 0.01) and haemoglobin (-2.58 +/- 0.72 g 100 ml-1, P < 0.05) were observed at 60 min post-bleeding. 3. Pretreatment with one or two specific antagonists did not exaggerate the initial fall in blood pressure. The initial bradycardia was weakened only by combined blockade with losartan and AVPX. 4. The blood pressure recovery from a haemorrhage was delayed by approximately 25 min by the inhibition of vasopressin activity. The systolic blood pressure recovery in control animals (81% of the acute fall) was blunted by losartan (55% of the acute fall), prazosin (49%), combined losartan and AVPX (36%), prazosin and AVPX (36%), and also by prazosin plus losartan (13%). The diastolic blood pressure recovery was blunted only in the groups where the activity of angiotensin II was inhibited by losartan. 5. In conclusion, we have shown that neither catecholamines, angiotensin II nor vasopressin, although activated, individually compensate the acute hypotensive response to haemorrhage. The contribution of vasopressin to the blood pressure recovery post-bleeding is transient and is rapidly replaced by the pressor activity of the catecholamines and angiotensin II. The full systolic blood pressure recovery from severe haemorrhage requires the combined activity of these two pressor systems, while the diastolic blood pressure recovery seems to be only dependent upon angiotensin II activity.     

Platelet lipoxygenase in spontaneously hypertensive rats

We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.     

Sulfhydryl group donors potentiate the hypotensive effect of acetylcholine in rats

Nitric oxide mediates the vasodilator and hypotensive responses of acetylcholine infusion. It has been reported that nitric oxide could be protected from free radical destruction by forming an S-nitrosothiol compound. Furthermore, sulfhydryl donors such as N-acetylcysteine or thiosalicylic acid enhance nitric oxide production from nitroglycerin. Consequently, the hypotensive effect of intravenous acetylcholine infusion might be potentiated during the simultaneous administration of sulfhydryl donors. The objective of the present study was to test in Okamoto spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (1) whether the hypotensive effect of acetylcholine (10 micrograms/kg per minute) was affected by the simultaneous administration of N-acetylcysteine (10 micrograms/kg per minute) or thiosalicylic acid (10 micrograms/kg per minute), and (2) whether NG-nitro-L-arginine-methyl ester (100 micrograms/kg per minute) administration was able to reverse the changes induced by acetylcholine plus N-acetylcysteine or acetylcholine plus thiosalicylic acid. The administration of acetylcholine reduced (P < .05) mean arterial pressure in WKY rats (13 +/- 2%) and SHR (14 +/- 2%) without affecting urine flow rate, urinary sodium excretion, and glomerular filtration rate. In the presence of N-acetylcysteine, the acetylcholine-induced reduction in mean arterial pressure was potentiated (P < .05) in WKY rats (24 +/- 4%) and SHR (20 +/- 2%). These changes in mean arterial pressure were accompanied by significant reductions in urine flow rate and urinary sodium excretion in WKY rats, as well as in glomerular filtration rate in SHR.2     

Blood pressure and heart rate response to apomorphine in urethane anesthetized rats

The mechanisms involved in the hypotensive effect of apomorphine were studied in urethane anesthetized rats. The intravenous injection of apomorphine (0.01-0.75 mg/kg) produced a dose dependent fall in mean blood pressure. At the higher doses used (0.5-0.75 mg/kg) a marked bradycardia accompanied the hypotensive effect. These cardiovascular effects were prevented by pretreating the animals with pimozide (0.01-0.1 mg/kg). Low doses of haloperidol (0.03-0.3 mg/kg) did not antagonize the hypotensive action of apomorphine. Higher doses of haloperidol (1-3 mg/kg) reduced markedly the mean blood pressure. Atropine (1 mg/kg) partially antagonized the decrease in mean blood pressure induced by apomorphine and prevented completely the bradycardia. Hexamethonium (10 mg/kg) reduced the mean blood pressure and when apomorphine was administered, a residual hypotensive effect and no bradycardia was observed. It is concluded that the cardiovascular actions of apomorphine are central in origin and mainly due to the stimulation of a dopamine receptor. A probable peripheral effect could not be discarded.     

Infantile hepatic hemangioendothelioma: the role of surgery

The antihypertensive effect of corilagin, one of the ellagitannins purified from the seeds of Euphoria longana Lam. (Sapindaceae), was investigated in the spontaneously hypertensive rat (SHR). Administration of corilagin into conscious SHR at 5 mg/kg produced an antihypertensive effect equivalent to that induced by 1 mg/kg of guanethidine. This dose-dependent hypotensive effect was comparable with that observed in anesthetized SHR animals. Corilagin did not modify the baroreflex sensitivity in phenylephrine-challenged SHR. Corilagin reduced plasma noradrenaline in a dose-dependent fashion, an effect that was maintained in adrenalectomized rats. Failure of the antagonists for alpha2-adrenoceptors, idazoxan and yohimbine, as well as for dopamine receptors, haloperidol and domperidone, to reverse the antihypertensive actions of corilagin ruled out the participation of these receptors. Moreover, corilagin attenuated the pressor effects of methoxamine and Bay K8644 to a similar degree, indicating the direct effect of corilagin on vascular activity in rats. These results suggest that corilagin possesses the ability to lower blood pressure through the reduction of noradrenaline release and (or) direct vasorelaxation.     

Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice

In previous studies, we demonstrated that in ANG II-treated rats, prevention of cardiac hypertrophy (CH) by enalapril was blunted by bradykinin (BK) blockade by Hoe140. The putative role of BK was assessed by chronic exogenous BK infusion and in 46 male Sprague-Dawley rats infused with ANG II. ANG II (200 ng/kg/min) alone and associated with BK at low (BKlow, 15 ng/kg/day), mid (BKmid, 100 ng/kg/day) and high doses (BKhigh, 100 ng/kg/min) were delivered by Alzet osmotic pumps for 10 days and compared to control animals (Veh). Values of systolic arterial pressure (SAP, mmHg) in conscious rats and heart weight (HW, mg/g bw) at the end of the study are reported below. Results were submitted to ANOVA and are expressed as mean +/- SEM.     

The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity

OBJECTIVE: To investigate the metabolic effects of losartan (Cozaar) in patients with essential hypertension. METHODS: Twenty patients with mild hypertension (office blood pressure > 140/95 mmHg and home diastolic blood pressure > 90 mmHg) were examined in a double-blind, placebo-controlled cross-over study of 4 weeks of treatment with 50-100 mg losartan. The effects on glucose metabolism were assessed by euglycaemic glucose clamp examinations [glucose disposal rate (GDR, mg/kg per min)] and oral glucose-tolerance tests (OGTT). RESULTS: Supine blood pressure was reduced from 146 +/- 3/90 +/- 3 mmHg on placebo to 134 +/- 4/83 +/- 3 mmHg on losartan and the difference was maintained during 120 min of insulin infusion and glucose clamping. GDR was 6.2 +/- 0.5 mg/kg per min on placebo and 6.4 +/- 0.5 mg/kg per min on losartan. The glucose and insulin responses (the area under the curve) during OGTT were similar with placebo and losartan (0.86 +/- 0.3 versus 0.88 +/- 0.4 and 341 +/- 60 versus 356 +/- 60, respectively; arbitary units). Serum cholesterol was 5.3 +/- 0.2 mmol/l on placebo and 5.1 +/- 0.2 mmol/l losartan treatment. High-density lipoprotein cholesterol and triglycerides were, respectively, 1.1 +/- 0.1 and 1.5 +/- 0.2 mmol/l with placebo, and 1.1 +/- 0.1 and 1.4 +/- 0.1 mmol/l with losartan treatment. CONCLUSION: In mildly hypertensive patients, selective angiotensin II receptor antagonism with losartan for 4 weeks lowers blood pressure at rest and during 120 min of glucose clamping, and has neutral effects on insulin sensitivity, glucose metabolism and serum lipids.     

Effect of indomethacin on blood pressure control during treatment with nitrendipine

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.     

The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT1 receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg-1 body wt). Losartan (1 or 0.33 mg h-1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 +/- 0.84 mL kg-1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h-1 caused an early onset of the decompensation phase after only 9.8 +/- 0.8 mL kg-1 of blood loss compared with control. Intravenous infusion of losartan (1 mg h-1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 +/- 1.0 mL kg-1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT1 receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h-1 caused an early onset of the decompensation phase during haemorrhage at 11.06 +/- 0.91 mL kg-1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT1-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.     

Comparative antihypertensive effects of propranolol and metoprolol in DOC-treated rats

The effects of chronic twice daily s.c. injections of dlpropranolol, metoprolol and d-propranolol on systolic blood pressure and heart rate were assessed in conscious DOC-saline hypertensive rats. Measurements were taken (tail-cuff) 4 hr after the morning injection and 16-18 hr after the afternoon injection during 11 of 19 consecutive treatment days. Only dl-propranolol and metoprolol at 5 mg/kg lowered blood pressure and heart rate significantly relative to the changes occurring in control saline-injected animals. At the lower dose of 0.2 mg/kg, both agents tended to decrease heart rate while having little or no effect on blood pressure. The overall blood pressure and heart rate changes produced by propranolol at 5 mg/kg differed significantly from those of the control group at both the 4 and 16-18 hr post-dosing intervals. Metoprolol at 5 mg/kg produced significant overall changes in blood pressure and heart rate only at the 4 hr post-doing interval. D-propranolol had no effect on either blood pressure or heart rate. The results indicate tha s.c. propranolol and metoprolol lower systolic blood pressure in conscious DOC-saline hypertensive rats only at the higher dose of 5 mg/kg and that cardioselectivity does not afford increased antihypertensive activity in this model.     

Role of kinins in the acute antihypertensive effect of enalapril in hypertensive rats

1. We used the kinin antagonist HOE 140 to investigate the role of endogenous kinins in the acute antihypertensive effect of the angiotensin converting enzyme inhibitor enalapril in chronic and acute renal hypertensive rats. 2. In normotensive rats, treatment with HOE 140 (33 micrograms/kg, sc) caused a complete blockade of the depressor effect of bradykinin (100 ng, ia) without affecting the depressor effect of sodium nitroprusside (1 microgram, i.v.) or the basal blood pressure. 3. HOE 140 treatment (33 micrograms/kg, sc, plus 330 ng/min, i.v.) did not affect basal blood pressure of chronic (6-7 weeks) one-kidney, one clip and two-kidney, one clip hypertensive rats and in rats with acute hypertension, elicited by unclamping the renal pedicle that had been occluded for 5 h, but HOE 140 completely blocked the hypotensive response to bradykinin (100 ng, ia) during the 60-min period after enalapril administration (2 mg/kg, i.v.). 4. Acutely hypertensive rats treated or not with HOE 140 (33 micrograms/kg, sc, plus 330 ng/min, i.v.) presented a similar fall in blood pressure after enalapril (165 +/- 5 to 137 +/- 6 mmHg and 166 +/- 5 to 136 +/- 6 mmHg, respectively). 5. Untreated two-kidney, one clip hypertensive rats presented a rapid and sustained fall in blood pressure after enalapril (177 +/- 4 to 148 +/- 4 mmHg) that did not differ from the HOE 140-treated (33 micrograms/kg, sc, plus 330 ng/min, i.v.) group (177 +/- 6 to 154 +/- 4 mmHg). 6. One-kidney, one clip hypertensive rats treated with HOE 140 (33 micrograms/kg, sc, plus 330 ng/min, i.v.) showed a significantly smaller fall in blood pressure after enalapril (204 +/- 7 to 179 +/- 9 mmHg) compared to the untreated rats (197 +/- 7 to 149 +/- 2 mmHg). 7. These results indicate that kinin potentiation plays an important role in the antihypertensive effect of acutely administered angiotensin converting enzyme inhibitor in the one-kidney, one clip model of hypertension.     

Zaprinast, but not dipyridamole, reverses hemodynamic tolerance to nitroglycerin in vivo

Hemodynamic tolerance to nitroglycerin was developed in spontaneously hypertensive rats following 2-3 days of pretreatment with 100 mg/kg of nitroglycerin administered s.c. 3 times/day. Tolerance was evaluated both in vivo, by administering ascending bolus doses of nitroglycerin of 1-300 micrograms/kg i.v., and ex vivo in isolated, denuded aortic vascular rings by exposure to ascending concentrations of nitroglycerin of 0.0003-100 microM. Tolerance was observed as a significant blunting of the hypotensive and vasorelaxant effect of nitroglycerin. Co-incubation of tolerant aortic rings and pretreatment of tolerant SHR with 10 microM and 0.1-10 mg/kg zaprinast, respectively, resulted in full restoration of the vasorelaxant and hypotensive effect of nitroglycerin. Zaprinast partially reversed hemodynamic tolerance at 0.01 mg/kg. Conversely, dipyridamole (10 microM) reversed tolerance ex vivo, but was ineffective in reversing tolerance in vivo at pretreatment doses of 30 and 60 mg/kg. Following a 100-micrograms/kg i.v. challenge dose of nitroglycerin, aortic cyclic guanosine monophosphate (cGMP) levels were lower in nitroglycerin tolerant SHR when compared to non-tolerant SHR. Pretreatment of tolerant SHR with 10 mg/kg zaprinast restored the increase in cGMP levels to nitroglycerin to that seen in non-tolerant SHR. Conversely, dipyridamole (30 mg/kg) pretreatment was not effective in restoring cGMP levels. These data therefore suggest that reversal of hemodynamic tolerance in vivo is related to restoration of changes in vascular cGMP levels. Zaprinast, a selective cGMP phosphodiesterase inhibitor, effectively reverses tolerance and dipyridamole, a rather non-selective inhibitor, does not.     

Relative bioavailability of carbinoxamine and phenylephrine from a retard capsule after single and repeated dose administration in healthy subjects

The present study was designed to investigate the role of cardiopulmonary reflex, more specifically the Bezold-Jarisch reflex, in experimental hypertension induced by chronic administration of Nw-nitro-L-arginine methyl ester (L-NAME) (0.5 mg/ml) added to the drinking water for 6 days. The study was performed in male Wistar rats (200-350 g), 9 animals per group. L-NAME ingestion caused a significant increase in resting mean arterial pressure (MAP: 182 +/- 4 mmHg) and heart rate (HR: 447 +/- 20 bpm) when compared to untreated rats (MAP: 112 +/- 3 mmHg and HR: 355 +/- 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 micrograms/kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. As expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 +/- 14 to 175 +/- 25 bpm) and DAP (from 7 +/- 4 to 39 +/- 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30%). These data suggest that, in contrast to other models of hypertension, in the present one caused by inhibition of nitric oxide synthesis, the Bezold-Jarisch reflex is exaggerated. This neural dysfunction could be related to changes in the cardiac vagal efferent or effector.     

Blood pressure and renin activity in essential hypertension under pindolol

20 essential hypertension patients with diastolic blood pressure of 100-140 mm Hg were treated with increasing doses (15-45 mg/day by mouth) of pindolol for 14 weeks after an initial placebo period of 5 weeks. Systolic and diastolic blood pressure decreased significantly with as little as 15 mg of pindolol (p less than 0.001). No further changes in systolic and diastolic blood pressure were observed when the doses of pindolol were increased. Plasma renin activity (PRA) determined by radioimmunoassay did not change under increasing doses of pindolol. The blood pressure changes did not correlate with initial PRA or with individual changes in PRA under increasing doses with individual changes in PRA under increasing doses of pindolol. These results do not afford evidence for a renin-dependent hypotensive effect of pindolol.     

Lack of association between both insulin resistance and plasma insulin levels with blood pressure values in essential hypertension

AIM: To evaluate the role of insulin resistance and hyperinsulinaemia in the genesis of essential arterial hypertension (EAHT). SUBJECTS AND METHODS: We studied 49 patients (age 44 +/- 8 y., body mass index (BMI: 29.5 +/- 3.2 kg.m-2) with mild or moderate EAHT (systolic blood pressure: 156 +/- 13 mmHg, diastolic blood pressure: 100 +/- 6 mmHg). Patients with BMI > 27 kg.m-2 were classed as obese. Arterial pressure was measured with a mercury sphygmomanometer after the patient had been lying down for 15 min. For each patient, the results of a frequently sampled intravenous glucose tolerance test (FSIGT) were used to estimate insulin sensitivity (using the minimal model of glucose metabolism) and to characterize insulin secretion in response to intravenous glucose (area of the insulin curve above basal during the 180 min of the FSIGT test). Correlations were evaluated by means of Spearman's correlation coefficient. RESULTS: Neither fasting insulinaemia, glucose-induced insulin secretion nor insulin sensitivity correlated significantly with arterial pressure, either in the whole sample or in the obese and non-obese subsamples. CONCLUSIONS: These results suggest that neither insulin nor insulin sensitivity are important physiological regulators of arterial pressure, and lend no support to the hypothesis that insulin is related to essential arterial hypertension.     

The effect of a lesion of the subcortical conducting pathways on the electrical activity of the human cerebral cortex

We studied whether monophosphoryl lipid A (MLA), an endotoxin derivative, protected the heart from planned ischemia in hypercholesterolemic conscious rabbits. Normal and hypercholesterolemic (8-week exposure to 1.5% cholesterol-enriched diet) conscious rabbits with right ventricular electrode and left ventricular polyethylene catheters were subjected to ventricular overdrive pacing (VOP: 500 beats/min over 10 min = control VOP). The resulting intracavitary ST-segment elevation, increase in left ventricular end-diastolic pressure (LVEDP), and a reduction of ventricular effective refractory period (VERP) were measured. Three days later the animals were given a single intravenous bolus of 10 or 30 microg/kg MLA or its solvent or both, and a second VOP (test VOP) was applied 24 h later. MLA decreased ST elevation and LVEDP increase from 2.1 +/- 0.16 to 1.27 +/- 0.25 and 0.97 +/- 0.13 mV and 14.6 +/- 1.2 to 11.1 +/- 1.0 and 12.4 +/- 1.2 mm Hg in normal animals and from 2.55 +/- 0.14 to 1.31 +/- 0.12 and 0.96 +/- 0.30 mV and from 21.0 +/- 1.6 to 11.7 +/- 1.3 and 12.4 +/- 1.3 mm Hg in atherosclerotic animals after 10- and 30-microg/kg doses, respectively (p < 0.001 for each). VOP-induced VERP reduction was also significantly alleviated by both MLA doses; nevertheless, 30-microg/kg MLA significantly prolonged resting VERP with a slight VERP reduction in response to pacing in both normal and atherosclerotic animals. We conclude that MLA produces a delayed antiischemic effect in both normal and hypercholesterolemic/atherosclerotic conscious rabbits.     

The effect of chronic hypertension on skin blood flow

OBJECTIVE: To determine whether the cutaneous microvasculature of the spontaneously hypertensive rat (SHR) is affected by chronic hypertension. DESIGN: We used laser Doppler techniques to measure skin blood flow in 22 SHR and in 22 non-hypertensive Wistar-Kyoto (WKY) rats over a 1-year time span, beginning at age 3 months. Sites of measurement included the back, leg, and root of the tail, areas with a predominantly nutritive perfusion, and the plantar surface of the paw, which has a large contribution from large arterioles and venules. Flow was measured at basal skin temperature and at the maximally heat-stimulated condition of 44 degrees C. Systolic tail arterial blood pressures were measured concurrently. RESULTS: At baseline, systolic blood pressures were considerably higher in the SHR (190 +/- 4 mmHg) than they were in the WKY rats (138 +/- 2 mmHg). Skin blood flow values at the three nutritive sites were similar in the two species. However, at 44 degrees C, flow was significantly higher at the paw in the SHR (46.8 +/- 3.5 versus 34.3 +/- 2.2 ml/min per 100 g). We attribute this difference to the effect of high perfusion pressure on large arterioles. During the 1-year measurement period, there was no appreciable change in blood flow in the WKY rats. In contrast, the SHR showed a steady progressive decline in skin blood flow at all sites. The largest decline was at the paw with a rate of fall of about 2.4%/month. After 1 year, there was no difference between paw blood flow in the SHR (27.5 +/- 1.8 ml/min per 100 g) and in the WKY rats (27.6 +/- 1.9 ml/min per 100 g). CONCLUSIONS: Skin blood flow reserve falls in response to chronic hypertension. The rate of fall is greater at sites with significant arteriovenous perfusion that at nutritive sites.     

Microalbuminuria in essential hypertensives in treatment for hypertension

Urinary albumin excretion (UAE) was evaluated in 26 subjects with essential hypertension and no diabetes (5 men, 21 women; 19 whites and 7 blacks), with creatinine clearance (Ccreat) > or = 75 ml/min/1.73 m2, in individualized treatment with various antihypertensive drugs. Clinical and laboratorial data were the following: mean age, 53 +/- 2 years (SEM); duration of hypertension, 14.9 +/- 2.2 years; body mass index (BMI), 26.8 +/- 0.7; arterial blood pressure, 142 +/- 4/89 +/- 3 mmHg; serum creatinine, 0.8 +/- 0.03 mg/dL; Ccreat, 99.3 +/- 3.8 ml/min/1.73 m2 and UAE, 9.3 +/- 1.5 micrograms/min. No significant difference was found when data were evaluated for gender and race. Microalbuminuria, defined as UAE > 13.9 micrograms/min, was found in 19% of the hypertensives (range: 16.3 to 28.1 micrograms/min). UAE correlated positively and significantly with systolic (r = 0.6309; P = 0.0005), diastolic (r = 0.4146; P = 0.0352), and mean blood pressure (r = 0.5000; P = 0.0093). The correlation between UAE and systolic pressure was stronger than with diastolic pressure. There was a positive and significant correlation between BMI and UAE values (r = 0.5623; P = 0.0028), and between BMI values with those of systolic (r = 0.5271; P = 0.0057) and mean blood pressure (r = 0.3930; P = 0.470). No correlation was found between UAE and age, duration of hypertension or Ccreat. Systolic, diastolic and mean blood pressures were significantly higher in microalbuminuric than in non microalbuminuric hypertensives. Obese hypertensives presented higher mean values of UAE, systolic, diastolic and mean pressures than non obese.