Factors influencing plasma renin and angiotensin II in the conscious pregnant ewe and its foetus

1. Plasma renin (measured in the presence of additional substrate) was significantly higher (10.7 +/- 1.1 S.E. of mean ng/ml.hr) in foetal lambs of 111-144 days gestation age (full term 147 days) than in their mothers (1.5 +/- 0.2 ng/ml.hr S.E. of mean, P < 0.001) but plasma angiotensin II concentrations were in the same range (ewe 47.3 +/- 6.6 S.E. of mean, foetus 47.4 +/- 14.1 S.E. of mean pg/ml.). The endogenous velocity of renin production by foetal plasma was also greater than that of maternal plasma.2. Foetal plasma [Na(+)] (137 +/- 0.8 S.E. of mean m-equiv/l.), was lower than that in the ewe (142 +/- 1.5 m-equiv/l. S.E. of mean, P < 0.01).3. Foetal plasma renin in lambs of less than 120 days gestation was lower (9.2 +/- 2.7 S.E. of mean ng/ml.hr) than that in lambs of over 130 days gestation (12.6 +/- 2.6 ng/ml.hr S.E. of mean, P < 0.01). Foetal plasma [K(+)] (3.8 +/- 0.1 S.E. of mean m-equiv/l.) was also lower in lambs of less than 120 days gestation than in those over 130 days (4.1 +/- 0.1 S.E. of mean m-equiv/l., P < 0.001).4. When small volumes of blood (相似文献   

Angiotensin II-like activity in circulating arterial blood in immature and adult rabbits

1. Angiotensin II-like activity was estimated from the contraction of the rat ascending colon superfused with arterial blood in an extracorporeal circuit. The colon was calibrated by infusion of synthetic angiotensin II amide (Hypertensin, CIBA Ltd).2. Resting levels of angiotensin II-like activity were obtained by comparison of the length of a rat colon preparation superfused alternately with blood from an intact and from a nephrectomized rabbit.3. The resting levels of angiotensin II-like activity reached a maximum value of about 1.6 ng/ml. at 10-14 days of age, and thereafter declined to the adult value of 0.23 ng/ml. Rabbits of less than 100 g body weight had resting levels in the same range as adults.4. Removal of 25% of the calculated blood volume induced five times greater increments in arterial angiotensin II-like activity in immature than in adult rabbits (1.68 +/- 0.26 S.E. of mean ng/ml. compared with 0.34 +/- 0.08 S.E. of mean ng/ml.).5. No evidence was obtained that the high levels of angiotensin II-like activity encountered in immature rabbits were attributable to a slower rate of inactivation of angiotensin by tissues.6. The pronounced activity of the renin-angiotensin system demonstrated by these experiments in immature rabbits especially during haemorrhage is consistent with the suggestion that this system is of particular importance in cardiovascular control in early life.     

The specific influence of carbon dioxide and carbamate compounds on the buffer power and Bohr effects in human haemoglobin solutions

1. Lymph from the lungs of lambs and sheep was found to enter both the right lymph duct and the thoracic duct. Right lymph duct flow was collected by constructing a venous sac, the venous tributaries of which were ligated but which the right lymph duct entered; thoracic duct flow was collected by cannulating the duct. Lymph from sites other than the lungs was excluded from the collections.

2. Measurements were made of the surface tension characteristics of lung extracts and of the liquid present in foetal lungs. These values were used together with gestational age and crown-rump length to designate the foetal lambs into mature and immature groups.

3. Lymph flow from the lungs averaged 0·99 ml./kg body wt./hr in immature foetal lambs, and 1·81 ml./kg/hr in mature foetal lambs before the start of ventilation. Lymph flow from the lungs of spontaneously delivered new-born lambs (mean age 51 hr) averaged 0·86 ml./kg/hr. In adult ewes right lymph duct flow averaged 0·11 ml./kg/hr and total lung lymph flow was estimated indirectly to be 0·33 ml./kg/hr. Calculated rates of protein flow in lung lymph (flow × protein concentration) were greater in foetal lambs than in adult sheep.

4. Total thoracic duct flow averaged 2·48 ml./kg/hr in immature foetal lambs, 5·30 ml./kg/hr in mature foetal lambs, 3·65 ml./kg/hr in new-born lambs, and 2·92 ml./kg/hr in adult ewes.

5. At the start of ventilation there was an increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6·4 ml./kg/hr in mature lambs and 2·6 ml./kg/hr in immature lambs. At the same time the protein concentration of lymph decreased but the calculated protein flow increased.

6. The lungs of foetal lambs weighed more than the lungs of spontaneously delivered new-born lambs, and the difference could be accounted for by liquid which could be aspirated through the trachea of the foetal lamb. On ventilation of the lungs for 2 hr, without first allowing the escape of any lung liquid, lung weight measurements indicated that about 66% of the lung liquid had been taken up in mature lambs and about 50% in immature lambs.

7. It was concluded that the rate at which lymph is formed in the lungs is greater per kilogram body weight in foetal than in new-born lambs and greater in them than in ewes. The increase in lymph flow at the start of ventilation could account for the removal of about 40% of the liquid present in the lungs of the mature foetus and about 25% of the liquid in the lungs of the immature foetus.

     

The effect on drinking in the rat of intravenous infusion of angiotensin, given alone or in combination with other stimuli of thirst

1. Intravenous infusion of angiotensin causes rats which are in water balance to drink water.2. The mean amount of angiotensin needed to initiate drinking was 29.1 +/- 4.6 mug/kg (S.E. of mean) in twenty normal rats, and 15.7 +/- 2.1 mug/kg in thirty-four nephrectomized rats.3. The nephrectomized rat is therefore more sensitive to this action of angiotensin than the rat with intact kidneys.4. The rates of infusion (0.05-3.0 mug/kg(-1) min(-1)) which cause drinking are comparable to those used to produce other effects in rats.5. Angiotensin restores the drinking response of the nephrectomized rat subjected to caval ligation to a value similar to that obtained in the uninfused normal rat subjected to caval ligation.6. The effects of angiotensin and hypertonic saline on drinking are additive when both substances are administered to nephrectomized rats.7. These experiments provide further support for the view that the renin-angiotensin system is concerned in extracellular thirst.     

Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice

The present experiments were performed to determine the influence of intravenous administration of renin substrate on plasma angiotensin II levels and mean arterial blood pressure in conscious C57BL/6J mice. Mice with chronic indwelling femoral arterial and venous catheters were acutely or chronically administered intravenous doses of a synthetic peptide corresponding to the 14 amino acids on the N-terminal of angiotensinogen. A dose-dependent increase in arterial blood pressure was observed as the intravenous bolus dose of the renin substrate was increased from 0.18 to 180 nmol kg(-1) with a maximal increase in pressure of 40 +/- 3 mmHg achieved following administration of the 18 nmol kg(-1) bolus (n = 11). Additional experiments demonstrated that a sustained intravenous infusion of the renin substrate led to a long-term increase in arterial blood pressure. The continuous infusion of renin substrate at 0.05 nmol kg(-1) min(-1) for 3 days did not alter arterial blood pressure from the control level of 119 +/- 5 mmHg (n = 5); however, arterial blood pressure significantly increased to 129 +/- 6 mmHg with an infusion rate of 0.5 nmol kg(-1) min(-1) and further increased to 141 +/- 3 mmHg when the renin substrate infusion was increased to 5.0 nmol kg(-1) min(-1). Finally, the infusion of renin substrate at 5.0 nmol kg(-1) min(-1) resulted in a significant increase in plasma angiotensin II concentration from 34 +/- 6 pg ml(-1) in vehicle-infused mice to 288 +/- 109 pg ml(-1). These results demonstrate that modulation of the circulating level of angiotensinogen can alter the plasma angiotensin II level and arterial blood pressure in normal animals.     

Foetal placental blood flow in the lamb

1. Fifteen sheep foetuses of 1.5-5.2 kg body weight were prepared with indwelling arterial and venous catheters for experimentation one to six days later.2. Unanaesthetized foetuses were found to have mean arterial and central venous blood pressures of 40 +/- 1.5 (S.E. of mean) and 2.0 +/- 0.3 (S.E. of mean) mm Hg respectively, compared to intra-uterine pressure. Intra-uterine pressure was 16 +/- 0.8 (S.E. of mean) mm Hg with respect to atmospheric pressure at mid-uterine level.3. Mean placental blood flow of the foetuses was 199 +/- 20 (S.E. of mean) ml./(min.kg body wt.). Mean cardiac output in eleven of the foetuses was 658 +/- 102 (S.E. of mean) ml./(min.kg).4. Mean foetal and maternal colloid osmotic pressures were 17.5 +/- 0.7 (S.E. of mean) and 20.5 +/- 0.6 (S.E. of mean) mm Hg respectively at 38 degrees C.5. Intravenous infusions into six ewes of 1.8 mole of mannitol and 0.4 mole of NaCl resulted in significant increases in foetal plasma osmolarity, sodium, potassium, and haemoglobin concentrations, without detectable transfer of mannitol to the foetal circulation.6. In the sheep placenta there is osmotic and hydrostatic equilibration of water. As a consequence, there should be an interaction between foetal placental blood flow and foetal water exchange with the maternal circulation. It was concluded that this interaction tends to stabilize foetal placental blood flow.     

Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions

Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions.     

Thyroxine utilization in the new-born lamb

1. From previous studies on foetal thyroid function in various mammalian species it would appear that the foetal pituitary-thyroid axis is capable of function before birth. Few studies are available to indicate the level of function before birth and in the immediate post-natal period.2. Plasma thyroxine levels, thyroxine pool and utilization rate of thyroxine have been followed in new-born Welsh mountain lambs from birth to 39 days of age.3. Plasma thyroxine levels are high within the first hour of life after birth (18.2 +/- 2.0 mug/100 ml.) and fall steadily to a minimum of 5.1 +/- 1.1 on day 11 and 12 of post-natal life. Thereafter they fluctuate about a mean of 6.1 mug/100 ml. The significance of these changes is discussed in respect to foetal thyroxine levels, placental permeability to thyroxine, and foetal and neonatal thyroid and pituitary function.4. Thyroxine utilization rate is high both in absolute terms and relative to unit body weight on days 1-4 of post-natal life. The utilization rate/kg remains fairly constant from days 10-39 of post-natal life.5. Thyroxine utilization in the new-born lamb is compared with that in the new-born calf in which the post-natal growth curve is very different.6. The various factors such as levels of free thyroxine, diet and environmental changes which influence thyroxine utilization are discussed and the rate of utilization is compared with other indices of thyroid function in new-born and adult animals of different species.     

Prorenin and active renin concentrations in plasma and ascites during severe ovarian hyperstimulation syndrome

The pathophysiology of ovarian hyperstimulation syndrome (OHSS) remains unclear. Several lines of evidence indicate that OHSS is associated with a stimulation of the renin-angiotensin system (RAS), but its functional significance as well as its role in the pathogenesis of the syndrome are not yet determined. OHSS is associated with high plasma and ascitic concentrations of total renin, renin activity (RA) and angiotensin II (Ang II). Their ovarian or renal origin is, however, still a matter of debate. To clarify these issues further, total renin, active renin, prorenin, RA and aldosterone were measured in plasma and ascites of nine patients who developed severe OHSS after in-vitro fertilization. Blood and ascites were sampled simultaneously during therapeutic paracentesis. Total renin and prorenin concentrations were significantly higher in the ascites (mean concentration +/- SE respectively of 5920 +/- 1430 mIU/l and 5250 +/- 1350 mIU/l) than in the plasma (respectively 3060 +/- 740 mIU/l and 2000 +/- 460 mIU/l) (P = 0.020 and 0.017 respectively). Conversely, active renin and RA concentrations tended to be lower, although not statistically significantly so in the ascites (respectively 670 +/- 190 mIU/l and 47 +/- 11 ng Ang I/ml/h) than in the plasma (respectively 1060 +/- 370 mIU/l and 75 +/- 21 ng Ang I/ml/h). Aldosterone concentrations were significantly higher in the serum (2609 +/- 374 pg/ml) than in the ascites (2025 +/- 347 pg/ml) (P = 0.015). The concentration gradient between plasma and ascites for total renin and prorenin supports the hypothesis of their ovarian origin in ascites and, to a large extent, in plasma, while it is likely that the high plasma active renin and RA concentrations reflect a peripheral activation of the RAS. In conclusion, the present findings are consistent with a marked stimulation of both ovarian and renal RAS during OHSS.      

Angiotensin II in human seminal fluid

The renin-angiotensin system (RAS) and angiotensin II are important in sperm function and male fertility. Angiotensin II type I (AT1) receptors have been identified in developing and ejaculated human spermatozoa, and angiotensin can stimulate sperm motility, the acrosome reaction and binding to the zona pellucida. However, there is little information on the availability of the hormone to spermatozoa during the reproductive process. Seminal plasma and blood plasma obtained from normal and subfertile subjects was extracted, and angiotensin content was analysed by radioimmunoassay. Values obtained for blood angiotensin II were within the normal range at 16.0 +/- 3.1 pg/ml (mean +/- SEM). Values for seminal plasma were usually 3-5 fold higher, at 51.6 +/- 9.3 pg/ml (n = 34, P < 0.0001). High performance liquid chromatography analysis showed that approximately 80% of the immunoreactive angiotensin was attributable to angiotensin II itself. However, seminal plasma angiotensin II concentrations were not correlated with blood angiotensin II, sperm concentration or sperm motility. The results show that immunoreactive angiotensin from a source other than the circulation is available to spermatozoa in human ejaculates. The results are consistent with the concept that angiotensin II has an important role in male fertility.     

The development of a blood-brain barrier mechanism in foetal sheep

1. The penetration of a metabolically inert, small molecular radius lipid insoluble substance ([(13)C] and [(4)H]sucrose), from blood into brain and c.s.f., has been studied in developing sheep from 50 days gestation (term, 150 days) through to the new-born stage. Around 50 days gestation sucrose accumulated rapidly into brain and c.s.f., and reached a steady-state level in brain of about 12% of the plasma level by 3 hr. By 60 days sucrose penetrated less freely into brain and c.s.f.; the brain steady-state level was 10% by 4(1/2) hr. A large decrease in sucrose penetration occurred by 70 days gestation, and by 123 days (just before the time when a foetal lamb becomes viable) both the rate of penetration and the brain steady-state level of sucrose were similar to those of the adult of other species.2. The rate of c.s.f. secretion at different ages has been estimated by dye dilution during ventriculo-cisternal perfusion. The turnover of c.s.f. in 60 day foetuses was high (1.36%/min.g wet weight brain). From 123 days gestation to the adult stage the turnover was much lower, 0.02%/min.g at 123 and 137 days gestation and 0.01%/min.g in the adult ewe.3. A simple new method for measuring c.s.f. volume is described. The volume at 51 days was estimated to be 0.14 ml., S.E. +/- 0.03, n = 4 (brain weight = 0.87 g +/- 0.11), at 59 days it was 0.45 ml., S.E. +/- 0.04, n = 6 (brain weight = 2.0 g +/- 0.1) and near term it was 7.28 ml S.E. +/- 1.29, n = 4 (brain weight 42.0 g +/- 0.5).4. The results are discussed in relation to possible changes in permeability of the cerebral capillary endothelium, the sink effect of c.s.f., and changes in extracellular space of the brain during its development. It is concluded that the high rate of penetration and raised brain steady-state level of sucrose in immature sheep foetuses is probably due to immaturity of a permeability barrier at the level of the cerebral capillary endothelium or its associated glial processes. Some clinical implications of these findings are considered briefly.     

Blood pressure maintenance in awake dehydrated rats: renin, vasopressin, and sympathetic activity

The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.     

Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion.

The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.     

Plasma immunoreactive atrial natriuretic factor is inhibited by selective blockade of alpha 2-adrenergic receptors in conscious Sprague-Dawley rats

Effects of alpha 2-adrenergic receptors and calcium channel blockade on basal and clonidine-stimulated immunoreactive atrial natriuretic factor (IR-ANF) in conscious Sprague-Dawley rats were evaluated. Clonidine was injected intravenously (i.v.) in a dose of 50 micrograms. Yohimbine and verapamil were used as a pretreatment, with clonidine in a dose of 50 micrograms and 0.5 mg respectively. The effects of yohimbine (1, 20, 50 micrograms) and verapamil (0.5 mg) on basal IR-ANF were also studied. Plasma IR-ANF was measured by radioimmunoassay with prior extraction on heat-activated Vycor glass. Clonidine injection in a dose of 50 micrograms caused a marked increase of plasma IR-ANF from 34.0 +/- 7.0 pg/ml (mean +/- S.E.M.) to 457.1 +/- 66.3 pg/ml. Clonidine-stimulated ANF secretion was partially inhibited by yohimbine from 457.1 +/- 66.3 pg/ml (mean +/- S.E.M.) to 99.9 +/- 23.1 pg/ml. Moreover, yohimbine in highest doses (50 micrograms) decreased the basal plasma IR-ANF from 34.0 +/- 7.0 pg/ml (means +/- S.E.M.) to 6.8 +/- 3.6 pg/ml. Verapamil did not alter basal and clonidine stimulated IR-ANF. These results indicate the important role played by alpha 2-adrenergic receptors in mediating ANF release.     

The renin-angiotensin system in foetal lambs

Summary Release of renin from the kidney in response to administration of frusemide was studied in foetal lambs, pregnant ewes and non-pregnant ewes. Plasma renin concentration rose to a greater extent in the foetus as compared with adult animals. The foetal kidney was capable of releasing renin at 110 days gestation.The greater responsiveness of the foetal kidney to natriuretic administration in terms of renin release may indicate a role for the renin angiotensin system in the maintenance of foetal circulatory homeostasis.     

Vasomotor responses in the hind limbs of foetal and new-born lambs to asphyxia and aortic chemoreceptor stimulation

1. Hind limb blood flow was measured in lambs of from 91 days gestation (delivered by Caesarean section) to 1 month after birth (term is about 147 days), under chloralose anaesthesia. Vascular resistance/100 g wet wt. increased progressively with age. There was reflex femoral vascular tone from the earliest age studied, as shown by vasodilatation on cutting the sciatic nerve.

2. On asphyxia by cord occlusion reflex femoral vasoconstriction began earlier and was somewhat greater in older foetal lambs. At all ages, and after denervation of the hind limb, there was vasodilatation after local ischaemia, and a vasoconstriction of delayed onset during asphyxia attributed to release of noradrenaline into the circulation. The vasoconstrictor effect of noradrenaline in immature lambs was at least as great as at term or in the new-born.

3. Injections of minimal effective doses of cyanide were used to localize possible chemoreceptor sites in foetal lambs. Injection into the left atrium caused a rise of arterial pressure, femoral vasoconstriction and a complex change in heart rate (usually bradycardia) but rarely any respiratory movement. After atropine, cyanide caused a large tachycardia. All responses were much reduced or abolished by cervical vagotomy.

4. Injection of the same doses of cyanide into a jugular vein, the right ventricle, pulmonary or common carotid arteries of foetal lambs caused negligible cardiovascular or respiratory effects, whereas injection into the carotids of new-born lambs caused a profound hyperpnoea.

5. It is concluded that the aortic chemoreceptors are active in the foetus, are supplied from the left heart, and that they probably represent the primary defence in blood gas homeostasis by their effects on the circulation.

     

Accentuated vascular and endocrine response to SQ 20881 in hypertension.

We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.     

Interaction of renal beta 1-adrenoceptors and prostaglandins in reflex renin release

Anesthetized dogs with isolated carotid sinus preparation were used to examine the mechanisms involved in the increase in renin secretion rate produced by carotid baroreceptor reflex renal nerve stimulation (RNS) at constant renal perfusion pressure. Lowering carotid sinus pressure by 41 +/- 5 mmHg for 10 min increased mean arterial pressure and heart rate, caused no or minimal renal hemodynamic changes, decreased urinary sodium excretion, and increased renin secretion rate. Metoprolol, a beta 1-adrenoceptor antagonist, given in the renal artery, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,764 +/- 525 to 412 +/- 126 ng/min (70 +/- 8%). Indomethacin or meclofenamate, prostaglandin synthesis inhibitors, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,523 +/- 416 to 866 +/- 413 ng/min (51 +/- 18%). Addition of metoprolol to indomethacin-pretreated dogs attenuated the increase in renin secretion rate from 833 +/- 327 to 94 +/- 60 ng/min (86 +/- 10%). These results indicate that reflex RNS at constant renal perfusion pressure results in an increase in renin secretion rate that is largely mediated by renal beta 1-adrenoceptors and is partly dependent on intact renal prostaglandin synthesis. The beta 1-adrenoceptor-mediated increase in renin secretion rate is independent of and not in series with renal prostaglandins.     

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats.

Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 +/- 2 mmHg vs. 38 +/- 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 +/- 0.03 vs. 0.31 +/- 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 +/- 2 to 44 +/- 2 mmHg, P = 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 +/- 0.02-0.42 +/- 0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P = 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r = 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma catecholamine concentrations during a 72-hour aminophylline infusion in children with acute asthma

To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean +/- SEM, 14.1 +/- 1.3 to 16.1 +/- 1.1 micrograms/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 +/- 56.0 and 67.6 +/- 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 +/- 125.1 pg/ml for NE at 24 hours (p less than 0.05), and 214.9 +/- 57.8, 233.7 +/- 82.2, and 137.6 +/- 39.4 pg/ml for E at 2, 24, and 48 hours (p less than 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 +/- 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased (p less than 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly (p less than 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)