Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs

The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9 +/- 4.7 to 3.8 +/- 1.7 ng/ml/3 hr (p less than 0.05). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5 +/- 4.6 to 7.0 +/- 2.9 ng/ml/3 hr (p less than 0.05). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA (5.9 +/- 1.8 to 2.9 +/- 1.6 ng/ml/3 hr) (p less than 0.001). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.     

Circadian variation of carrageenan-paw edema in the rat

The circadian variation of carrageenan (carr)-induced paw edema was studied in sham-operated and adrenalectomized rats. The edema was produced by carr injection into the plantar tissue at 03:00, 09:00, 15:00 and 20:00 hr. In sham-operated rats the rate of appearance of maximal edema was much faster in the evening than in the morning: at 20:00 hr, it was obtained 2 hours after carr injection while at 09:00 hr it took 4 hours. At 03:00 and 15:00 hr, maximal edema was found respectively 2.5 and 4 hours after carr. In adrenalectomized rats, maximal edema at 4 hours of investigation was always larger than in sham-operated animals but the rate of appearance of edema did not change throughout the day as it was obtained 3 hours after carr administration. At 09:00 and 20:00 hr injection of hydrocortisone (HC) to adrenalectomized rats produce the same dose-dependent effect on the rate of formation of edema. However, to reproduce in adrenalectomized animals the rates of formation of edema similar to those obtained in sham-operated rats, an injection of 18 mg/kg HC was required at 09:00 hr while less than 2 mg/kg was needed at 20:00 hr. The results suggest that the circadian rhythm of carr edema is related to circadian variation in the corticosteroid system.     

Comparative effects of cardiac receptors and sinoaortic baroreceptors on elevations of plasma vasopressin and renin activity elicited by haemorrhage

Increases in plasma vasopressin and renin activity that occur in response to haemorrhage have been attributed in part to reflex effects from cardiac receptors and sinoaortic baroreceptors, but the relative importance of these different receptors in causing humoral changes during haemorrhage in conscious dogs has not been reported. We investigated this question by hemorrhaging 6 sham-operated (SO), 6 cardiac-denervated (CD), 4 sinoaortic-denervated (SAD), and 4 combined sinoaortic and cardiac-denervated (SACD), conscious dogs. Blood was removed at a rate of 0.9 ml/kg X min. Plasma vasopressin and renin samples were taken during a control period and after 10, 20, and 30 ml/kg of blood had been removed. Results (mean +/- SE) are shown in the tables below. (table; see text) These experiments illustrate that: resting plasma levels of vasopressin and renin in conscious dogs are unaffected by the denervation procedures used in these experiments, the increase in plasma vasopressin that occurs during haemorrhage is mediated largely via cardiac receptors, with a considerably smaller contribution from the sinoaortic baroreceptors, during moderately severe haemorrhage (30 ml/kg) vasopressin secretion can be increased by a mechanism independent of sinoaortic and cardiac reflexes, the increase in plasma renin activity that occurs during haemorrhage is not dependent upon either cardiac or sinoaortic reflexes.     

19-hydroxyandrostenedione and 6 beta-hydroxyandrostenedione: new steroids regulated by the renin-angiotensin system in man

The changes of plasma 19-hydroxyandrostenedione (19-OH-A-dione) and 6 beta-hydroxyandrostenedione (6 beta-OH-A-dione) during the infusion of angiotensin II were evaluated and were compared with those of plasma aldosterone in man. Angiotensin II was infused into 5 normal subjects with an infusion pump at rates of 0.5, 1.0, 2.0 and 4.0 ng/kg per min. Each dose was infused for 20 min. Plasma 19-OH-A-dione rose significantly following the infusion of angiotensin II at a rate of 0.5 ng/kg per min and plasma 6 beta-OH-A-dione rose significantly following the infusion of angiotensin II at a rate of 1.0 ng/kg per min. In contrast, plasma aldosterone did not change significantly until the infusion rate reached 4.0 ng/kg per min. These results indicate that the secretion of 19-OH-A-dione and 6 beta-OH-A-dione is under the control of angiotensin II and the release of 19-OH-A-dione and 6 beta-OH-A-dione is induced earlier by the smaller doses of angiotensin II prior to the secretion of aldosterone. As 19-OH-A-dione and 6 beta-OH-A-dione amplify the action of aldosterone in bioassays using adrenalectomized rats and work as sodium-retaining and hypertensinogenic agents in intact rats, they are newly recognized biologically active steroids which are regulated by the renin-angiotensin system in man.     

Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake

Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 μg PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml(-1)·h(-1) (P < 0.05), whereas the median PTHrP + NaCl PRA value was normal (7.82 ng Ang I·ml(-1)·h(-1), P < 0.05 vs. PTHrP). Plasma Ca(2+) (median control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP + NaCl: 14.1 mg/dl; P < 0.05) and PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP + NaCl: 0.15 ng/ml; P < 0.05) were elevated in PTHrP- and PTHrP + NaCl-treated rats. Body weights and caloric consumption were lower in PTHrP- and PTHrP + NaCl-treated rats. NaCl consumption was lower in PTHrP-treated rats (mean Na(+): 28.5 ± 4.1 mg/day; mean Cl(-): 47.8 mg/day) compared with controls (Na(+): 67.3 ± 2.7 mg/day; Cl(-): 112.8 ± 4.6 mg/day; P < 0.05). NaCl consumption was comparable with control in the PTHrP + NaCl group; 0.3% NaCl in the drinking water had no effect on PRA in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA via its anorexic effects, reducing NaCl intake and causing NaCl restriction.     

Involvement of hypothalamic somatostatin in glucagon-induced suppression of growth hormone secretion in conscious rats

The role of central glucagon in regulating GH secretion was studied in conscious male rats with chronic indwelling intra-atrial and intracerebro-ventricular (ICV) cannulae. Repeated blood sampling every 20 min from 1000 hr to 1700 hr showed two major GH bursts occurring at regular intervals (3.6±0.1 hr) around 1200 hr and 1540 hr. The ICV (lateral ventricle) injection of glucagon (10 μg/rat) at 1100 hr inhibited spontaneous GH secretion, and the mean (±SE) plasma GH levels from 1120 hr to 1700 hr were lower than those in controls injected ICV with the vehicle solution only (31.9±7.8 ng/ml vs. 157.1±13.4 ng/ml, p<0.01). The GH bursts did not appear until 5 hr after the injection. The intravenous (IV) injection of glucagon (10 μg/rat) did not change plasma GH levels or the occurrence of spontaneous GH bursts. The glucagon-induced suppression of GH release was attenuated when anti-somatostatin serum (ASS), but not normal rabbit serum (NRS), was given IV in a volume of 0.25 ml immediately before the ICV injection of glucagon (10 μg/rat) (mean GH levels at 1120–1700 hr: ASS+glucagon, 133.6±26.7 ng/ml vs. NRS+glucagon, 30.5±7.4 ng/ml, p<0.01). These findings suggest that central glucagon may play an inhibitory role in regulating GH secretion by stimulating SRIF release from the hypothalamus in the rat.     

Dissociation of hyperreninemia and renal prostaglandin synthesis in the adrenalectomized rat

The aim of this study was to determine whether hyperreninemia in the adrenalectomized (ADX) rat is dependent on renal prostaglandin synthesis, as has been suggested for two other hyperreninemic conditions, Bartter's syndrome and chronic liver disease. Plasma renin concentration (PRC) in anesthetized, ADX rats was significantly increased (delta +480%; p less than 0.001) compared to sham-operated controls. In vivo, indomethacin (10 mg/kg i.v.) significantly reduced PRC of anesthetized, ADX rats after both 45 min (delta -34%; p less than 0.05) and 90 min (delta -47%; p less than 0.05). In vitro renin release from renal cortical slices of ADX rats was also significantly greater (delta +130%; p less than 0.05) than from sham-operated control cortical slices. Renin release from cortical slices of ADX rats given dexamethasone (10 micrograms/kg/day) for 4 days prior to sacrifice did not differ from sham-operated control values. Prostaglandin E2 (PGE2) release from cortical slices of ADX rats did not differ significantly from controls. However, PGE2 synthesis in glomeruli microdissected from ADX rats was significantly increased (delta +110%; p less than 0.001) compared to controls. PGE2 synthesis in glomeruli of dexamethasone-treated ADX rats remained significantly elevated compared to controls. Ibuprofen (10(-6) M) decreased PGE2 synthesis in cortical slices by 80%. However, prostaglandin synthesis inhibition had no effect on renin release from either ADX or control renal cortical slices. These results suggest that despite increased glomerular synthesis, prostaglandins do not directly influence renin release in the ADX rat.     

Oxytocin-induced renin secretion in conscious rats

Arterial hypotension and hypovolemia are known to stimulate neurohypophysial secretion of oxytocin (OT) in rats, although the physiological function of OT under these circumstances is uncertain. We now report that OT infused intravenously into conscious rats at 125 ng x kg(-1) x h(-1), a dose selected to mimic plasma OT levels during hypotension or hypovolemia, increased plasma renin concentration and plasma renin activity by twofold. This effect was prevented by systemic pretreatment with an OT receptor antagonist [[1-(3-mercaptopropionic acid)-2-O-ethyl-D-Tyr-Thr(4)-Orn(8)]-OT]. The OT antagonist did not block renin secretion induced by systemic injection of the beta-adrenergic receptor agonist isoproterenol, indicating that the OT antagonist does not interfere nonselectively with renin release. Pretreatment of rats with the beta-adrenergic receptor antagonist nadolol also prevented OT-induced renin secretion. Similarly, nadolol injected during infusion of OT markedly reduced the elevated plasma renin levels. These observations raise the possibility that pituitary OT secretion during hypotension or hypovolemia in rats may serve to support blood pressure by enhancing activation of the renin-angiotensin system via a beta-adrenergic receptor-dependent mechanism.     

Effect of indomethacin and propranolol on the blood pressure and renin response to atriopeptin III in conscious rats

The effect of prostaglandin synthesis inhibition and of beta-adrenoceptor blockade on the blood pressure and renin response to the synthetic atrial natriuretic peptide atriopeptin III was assessed in unanesthetized normotensive rats. This peptide was infused i.v. for 30 min at a rate of 1 microgram/min in rats pretreated either with indomethacin (5 mg i.v.) or propranolol (1 mg i.v.). The blood pressure reducing effect of atriopeptin III was attenuated neither by indomethacin nor by propranolol. Atriopeptin III per se did not modify plasma renin activity. Both the administration of indomethacin and of propranolol had a suppressing effect on renin release during atriopeptin III infusion. These data suggest that the vasodilating properties of atrial natriuretic peptides do not depend in the conscious normotensive rats on the production of prostaglandins. They also provide evidence that during infusion of such peptides, both prostaglandins and beta-adrenergic mechanisms are still involved in the regulation of renin secretion.     

The effects of ACTH1-24 or cortisol on pulmonary maturation in the adrenalectomized ovine fetus

Pulmonary maturation in 8 ovine fetuses bilaterally adrenalectomized at 98-101 days and infused at term with either ACTH1-24 or cortisol was compared with that in 4 untreated sham-operated controls. Four of the adrenalectomized fetuses were infused intravascularly with ACTH1-24 5 micrograms/h for 84 h before delivery and the other four were infused with cortisol 1 mg/h for 72 h. The high plasma concentrations of immunoreactive ACTH in the adrenalectomized fetuses (2762 +/- 1339 ng/l, mean +/- SD) were not significantly elevated by infusion of ACTH1-24 but were markedly depressed by infusion of cortisol. Distensibility (V40) of the lungs was less than that of controls in both the ACTH1-24-infused and cortisol-infused fetuses (1.86 +/- 0.31 ml/g vs 0.62 +/- 0.13 ml/g and 1.27 +/- 0.34 ml/g respectively) but it was significantly greater in the cortisol-infused fetuses compared to those infused with ACTH1-24. The volume of air retained at 5 cm H2O pressure (V5) during deflation was markedly reduced in adrenalectomized fetuses (controls 1.14 +/- 0.52 ml/g vs 0.25 +/- 0.25 ml/g and 0.12 +/- 0.6 ml/g). The wet weight of the lungs and the concentrations of saturated phosphatylcholine in lung tissue and lavage fluid were lower in the adrenalectomized fetuses than in controls but the differences were not significant. It is concluded that infusion of ACTH1-24 at term in adrenalectomized fetuses is probably without effect whereas cortisol enhances distensibility.     

Participation of substance P in the control of renin release.

The effect of the hypothalamic undecapeptide substance P on renin secretion rate was studied in the denervated dog kidney. Intrarenal infusion of substance P at a rate of 0.2 ng/kg/min suppressed renin secretion rates from 258.5 ± 28.5 ng/min to 133.1 ± 23.2 ng/min (p<0.001). Substance P infused at this dose neither changed blood pressure nor did it affect renal cortical plasma flow, glomerular filtration rate or sodium excretion. Thus, the suppression of renin release by substance P cannot be explained by any of the known control mechanisms. It is proposed that substance P participates in the control of renin release by a direct effect on the juxtaglomerular cells.     

The effect of oleate on pancreatic and bile secretion in the conscious rat

The effects of sodium oleate infused into either the duodenum or the terminal ileum on bile and pancreatic secretion were examined in the conscious rat. Rats were prepared with cannulae draining pure bile and pancreatic juice separately, and with an ileal and two duodenal cannulae. A 40 mM taurocholate solution containing 7 mg/ml bovine trypsin was infused into the duodenum throughout the experiment to replace diverted bile-pancreatic juice to maintain the normal regulation of pancreatic secretion. The intraduodenal infusion of sodium oleate significantly increased pancreatic juice flow, protein, and bicarbonate outputs, whereas it did not affect bile secretion. Intravenous infusion of proglumide (300 mg/kg/hr) did not inhibit pancreatic secretion stimulated by intraduodenal infusion of sodium oleate. An intravenous infusion of atropine (100 micrograms/kg/hr) attenuated protein and fluid secretions but not that of bicarbonate in response to intraduodenal oleate. In contrast, the intraileal infusion of oleate had no effect on pancreatic secretion, whereas it decreased bile flow, bicarbonate, and bile salt outputs. In conclusion, sodium oleate introduced in the duodenum stimulates pancreatic secretion but oleate in the terminal ileum inhibits bile secretion.     

Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats

We investigated the mechanisms underlying the protective action of glucocorticoids against indomethacin-induced gastric lesions. One-week adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) were administered indomethacin (25 mg/kg sc), and gastric secretion (acid, pepsin, and mucus), motility, microvascular permeability, and blood glucose levels were examined. Indomethacin caused gastric lesions in sham-operated rats, with an increase in gastric motility and microvascular permeability as well as a decrease in mucus secretion. Adrenalectomy significantly worsened the lesions and potentiated these functional disorders. Glucose levels were lowered by indomethacin in sham-operated rats, and this response was enhanced by adrenalectomy. The changes observed in adrenalectomized rats were prevented by supplementations of corticosterone at a dose mimicking the indomethacin-induced rise in corticosterone, whereas the protective effect of corticosterone was attenuated by RU-38486, a glucocorticoid receptor antagonist. We conclude that the gastroprotective action of endogenous glucocorticoids may be provided by their support of glucose homeostasis and inhibitory effects on enhanced gastric motility and microvascular permeability as well as maintaining the production of mucus.     

The effect of a neuropeptide Y antagonist, BIBP 3226, on short-term arterial pressure control in conscious unrestrained rats with congestive heart failure

The effects of a neuropeptide Y (NPY) Y1-receptor antagonist (BIBP 3226) on mean arterial pressure (MAP) and heart rate were investigated in conscious unrestrained rats with chronic congestive heart failure. The rats were randomly assigned to 2 groups, and received either BIBP 3226 or its inactive enantiomer (BIBP 3435) as an intravenous infusion (6 mg/kg/h for 1.5 h, respectively). Before, during and after the infusion, rats were stressed with a jet of air and received a bolus injection of NPY (2 nmol/kg iv.). There was no difference between the 2 groups in resting MAP and heart rate before, during or after infusion (BIBP 3226 vs. BIBP 3435). The effects of exogenous NPY on MAP were significantly attenuated in BIBP 3226 group during and 1 h after the infusion (p<0.05). The tissue NPY levels in heart, adrenal gland and kidney in heart failure rats were not different from those in sham-operated rats. The results suggest that Y1-receptor mechanisms are of minor importance in the short-term control of basal MAP and heart rate in conscious unrestrained rats with congestive heart failure.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

In vivo and in vitro studies of a putative inhibitor of cyclic guanosine 3',5'-monophosphate production.

Our main objective was to test the efficacy of 6-anilino-5,8-quinolinedione (LY83583) in vivo, a putative inhibitor of cyclic guanosine 3',5'-monophosphate (cGMP) production. If the drug proved capable of lowering plasma, vascular, and kidney levels of cGMP and of inhibiting the hypotensive effect of sodium nitroprusside and methacholine, then LY83583 could be of potential use in exploring the contribution of cGMP to cardiovascular and renal physiology. We found that when administered to trained conscious rats, LY83583 (1-mg/kg bolus, followed by a 2-hr infusion of 3 mg/kg.hr) decreased plasma cGMP concentration by 36% (P less than 0.01). Doubling the dosage of drug (2-mg/kg bolus, 6 mg/kg.hr) decreased plasma cGMP by 46% (P less than 0.05). We next measured tissue levels of cGMP ex vivo from rats that had received LY83583 or vehicle for 2 hr. The cGMP content of aortic segments when LY83583 was infused at the low dose, or renal cortical tissue when LY83583 was infused at both doses, was not significantly different from the cGMP content of tissue from rats that had received vehicle. LY83583 in doses up to 10-mg/kg bolus, followed by 6 mg/kg.hr infusion also failed to attenuate the hypotensive response to sodium nitroprusside or methacholine in conscious rats. Last, we tested whether, in our hands, LY83583 could reduce cGMP of aortic segments and kidney cortical slices in vitro. We found that after 10 min of incubation, 10(-5) M LY83583 decreased intracellular cGMP by approximately 65% and 50% in aortic and kidney tissues, respectively. In order to ascertain whether LY83583 lowered cGMP by stimulating phosphodiesterase, we incubated tissues with 10(-4) M 3-isobutyl-1-methylxanthine to inhibit the enzyme. In the presence of 3-isobutyl-1-methylxanthine LY83583 still exerted an inhibitory effect on cGMP production by aortic and kidney tissues. In conclusion, although LY83583 is a useful agent to lower renal and vascular tissues levels of cGMP in vitro, its efficacy in vivo seems doubtful.     

Cardiovascular effect of intravenously administered thyrotropin-releasing hormone and its concentration in push-pull perfusion of the fourth ventricle in conscious and pentobarbital-anesthetized rats

Changes in the concentration of thyrotropin-releasing hormone (TRH) in cerebrospinal fluid (CSF) were examined by the push-pull perfusion method after intravenous (i.v.) administration of the peptide in conscious and pentobarbital-anesthetized rats. The concentration of endogenous TRH in the perfusate was not changed during the 160-min perfusion period and was similar to that in the CSF (0.92 +/- 0.26 ng/ml) collected before the perfusion in conscious as well as in anesthetized rats. After i.v. administration of TRH (5 mg/kg) to the conscious rats, the peptide concentration in the perfusate increased to 42.23 +/- 14.33 ng/ml during the first 20 min and gradually returned to the basal level 2 hr after administration. The total amount of TRH detected in the perfusate was 20.0 ng. It was reduced by 75% in the anesthetized animals. The increases in blood pressure and heart rate, seen after i.v. as well as intracerebroventricular administration of TRH in the conscious rats, was significantly inhibited in the anesthetized rats. These results indicate that systemically administered TRH exerts its cardiovascular effect at central site(s), and that the transportation and the effect of the peptide is suppressed by pentobarbital anesthesia.     

Physiological responses to low dose infusions of atrial peptide in conscious dogs

Mongrel dogs prepared with chronic catheters in their femoral artery and vein and urinary bladder received 60 minute infusions of atrial peptide ranging from 5 to 100 ng/kg/min. Infusion of atrial peptides caused dose dependent increases in plasma atrial peptide concentration with doses of 25 ng/kg/min or less increasing plasma concentrations to levels observed in normal animals during stimulation of endogenous atrial peptide secretion. Atrial peptide infusion at doses of 10 ng/kg/min and above caused significant decreases in mean arterial pressure which were not accompanied by statistically significant changes in heart rate. Atrial peptide infusion at doses of 25 ng/kg/min and above increased urinary sodium excretion and urine flow rate. Atrial peptide infusion was without effect on plasma vasopressin, ACTH and corticosterone concentrations. However, atrial peptide infusion resulted in dose dependent decreases in plasma aldosterone concentration and plasma renin activity, but the decreases were only significant with the high physiologic (25 ng/kg/min) and pharmacologic doses (50 & 100 ng/kg/min). These data show that atrial peptide infusions in conscious dogs have minimal effects when infused in small doses that mimic endogenous atrial peptide release. At higher doses, significant effects on the cardiovascular, renal and endocrine systems can be observed but their physiological significance is unclear.     

Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion in hypophysial stalk-transected beef calves

The effects of growth hormone-releasing factor (GHRF) on growth hormone (GH) secretion were studied in beef calves after hypophysial stalk transection (HST). Peripheral GH concentration during surgery was elevated for 60 min after the initiation of anesthesia to 15 ng/ml, which was greater than plasma levels after HST and during the recovery period (0-30 hr mean, 3 ng/ml; P less than 0.05). Episodic GH secretion normally seen in sham-operated controls (SOC) was abolished after HST. Before HST, calves responded to 80% of the GHRF challenges, whereas after HST calves responded to every challenge of GHRF with an increase in plasma GH. A dose of 0.067 microgram human pancreatic (hp) hpGHRF(1-40)OH/kg body wt 3 days after HST increased plasma GH to 55 ng/ml from a control period mean of 5 ng/ml (P less than 0.04). On Day 8, HST calves received two injections of 0.067 microgram hpGHRF/kg body wt at 3-hr intervals, with feeding 70 min after the first injection. During two preinjection control periods, basal GH averaged less than 4 ng/ml and increased to 17 (P less than 0.02) and 9 (P less than 0.04) ng/ml immediately after the first and second injection of hpGHRF, but the response declined over the 8-day period after surgery. On Days 19 and 20, the HST calves were infused iv with 0.033 and 0.067 microgram somatostatin(SS)-14 (SRIH)/kg body wt, during which a pulse injection of 0.067 microgram hpGHRF/kg body wt was administered. GH increased to 9 and 5 ng/ml during the 0.033- and 0.067-microgram SRIH infusions after GHRF; no somatotropic rebound was observed after the SRIH was discontinued as was seen in the animals while the hypothalamic-hypophysial connections were intact. Five and six months after HST the responses to two analogs of rat hypothalamic GHRF were similar to those in SOC calves. These results indicate that HST calves responded to exogenous GHRF with an abrupt increase in plasma GH, but GH response to GHRF during SRIH infusion was greatly inhibited.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.