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Biomedical subjects

I A Reid

Publications and source records attributed to I A Reid.

At least 127 records · Page 7Linked to original sources
PubMed1976

The use of saralasin to evaluate the function of the brain renin-angiotensin system.

The demonstration that the components required for the generation of angiotensin II are present in the brain has led to the proposal that there is a brain renin-angiotensin system. To test this hypothesis, experiments were performed to determine if biologically active amounts of angiotensin II are formed when renin is injected into the cerebral ventricles. The effects of central administration of agents known to block the peripheral renin-angiotensin system were also investigated. It was shown that intraventricular renin increased water intake, blood pressure and ADH secretion and that these effects were blocked by saralasin. These findings indicated an interaction between injected renin, brain angiotensinogen and converting enzyme, resulting in the formation of angiotensin II in physiologically active concentrations. However, these experiments did not demonstrate a role for endogenous brain renin activity. Central administration of saralasin in normal animals did not decrease water intake, blood pressure or ADH secretion. These studies thus failed to demonstrate a physiological role for the proposed brain renin-angiotensin system in controlling water balance and blood pressure.

Angiotensin II↗
PubMed1975

Suppression of antidiuretic hormone secretion by clonidine in the anesthetized dog.

Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increases urine flow (V). In 11 anesthetized, hydropenic dogs, i.v. administration of clonidine (30 mug/kg) increased arterial pressure from 128 +/- 4 to 142 +/- 3 mm Hg and slowed heart rate from 138 +/- 7 to 95 +/- 7 beats/min within 30 min of injection; blood pressure then fell to 121 +/- 5 mm Hg 30 to 60 min after injection, and 112 +/- 5 mm Hg in the next 30-min period. V increased from 0.36 +/- 0.09 to 0.93 +/- 0.13 Uosm ml/min and urine osmolality (Uopsm) decreased from 1378 +/- 140 to 488 +/- 82 mOsm/kg of H2O 30 to 60 min following injection (P less than 0.001). These changes were accompanied by a decrease in TcH20. This increased V was not associated with increased glomerular filtration rate (GFR) or solute excretion, and occurred in acutely denervated kidneys and kidneys protected from the initial increase in arterial pressure by constriction of a suprarenal aortic clamp. By contrast, V TcH2O and UOsm were not altered by clonidine administration in seven acutely hypophysectomized dogs receiving a constant infusion of antidiuretic hormone (ADH) (80 muU/kg/min), despite similar hemodynamic changes produced by the drug. The results suggest that clonidine increases V through inhibition of ADH release, possibly via an indirect pathway mediated by the drug's alpha-adrenergic on the circulation.

Animals↗
PubMed1975

Parasympathetic pathways, renin secretion and vasopressin release.

1. The interrelationship between parasympathetic neural tone, renin secretion and vasopressin release was examined by observing the effect of bilateral cervical vagotomy on renin secretion in intact and acutely hypophysectomized dogs undergoing a water diuresis. 2. In intact dogs bilateral cervical vagotomy decreased the mean renin secretion from 1245 to 682 units/min (P less than 0.01) as urinary osmolality increased from 95 to 414 mosmol/kg (P less than 0.001). In contrast, in acutely hypophysectomized dogs cervical vagotomy failed to alter renin secretion significantly (834 to 893 units/min) and urinary osmolality was also unchanged (78 to 71 mosmol/kg). 3. The results suggest that a diminution in vagal tone may significantly alter renin secretion by stimulating vasopressin release. Exogenous vasopressin was associated with changes in urinary osmolality and renin secretion which were qualitatively similar to those seen after servical vagotomy. 4. We suggest that there is a neurohumoral reflex mechanism by which a fall in parasympathetic tone increases the release of vasopressin, which, in turn, suppresses renin secretion. The results are also compatible with the hypothesis that vasopressin inhibits renin release by a direct effect on the juxtaglomerular cells.

Animals↗
PubMed1975

Some central mechanisms of thirst in the dog.

Measurements of water intake were made on a population of trained conscious dogs of both sexes prepared with chronic third ventricle cannulae. 2. Injection of 100 ng angiotensin II into the third ventricle lead to a prompt stimulation of drinking, the mean water intake over a 5 min period being 503 +/- 89 ml. (n=6) compared with controls. This dipsogenic effect of angiotensin II was abolished by prior central administration of 10 mug saralasin acetate or 100 ng atropine. 3. Injection of 1 mug carbachol into the third ventricle produced a small, variable increase in drinking. 4. Injection of 0-2 ml. 5% NaCl into the third ventricle stimulated drinking, a response that was not affected by prior administration of 10 mug saralasin acetate or 100 ng atropine. 5. Following a 24 hr period of water deprivation there was an increase in plasma osmolality and plasma-renin activity. The drinking following this period of water deprivation was not affected by prior control administration of either 10 mug saralasin acetate or 100 ng atropine. 6. In two acute dogs, intracarotid infusion of 125I angiotensin II was not followed by significant appearance of radioactivity in the third ventricle or cisterna magna c.s.f. 7. The relevance of these results to the control of water intake is discussed.

Angiotensin II↗
PubMed1975

The effects of intracerebroventricular administration of renin on drinking and blood pressure.

The aim of the present investigation was to (a) determine if renin-substrate (angiotensinogen) is present in cerebrospinal fluid; (b) investigate the effects of intracerebroventricular administration of renin on drinking and blood pressure; and (c) determine if such effects are mediated via the formation of angiotensin II. Angiotensinogen concentration in cerebrospinal fluid was measured in 15 dogs and averaged 205 +/- 34 ng/ml. This value was approximately 1/5th of the corresponding plasma angiotensinogen concentration but the ratio of angiotensinogen:total protein in cerebrospinal fluid was approximately 15 times greater than in plasma. Intraventricular injection of hog renin (0.1 Goldblatt units) stimulated drinking in each of 8 dogs; the mean volume drunk in the 15 min period following the injection was 485 +/- 84 ml. When the renin was preceded by intraventricular saralasin acetate, a specific antagonist of angiotensin II, the drinking response was reduced to 8 +/- 6 ml. In eight pentobarbital anesthetized dogs, intraventricular dog or hog renin (0.05-0.25 Goldblatt units) increased systolic pressure from 152 +/- 10 to 168 +/- 10 mm Hg (P less than 0.001) and diastolic pressure from 101 +/- 8 to 116 +/- 7 mm Hg (P less than 0.001). This response, which lasted from 30 min to more than 3 h, was also abolished by saralasin acetate. These data indicate that centrally administered renin increases drinking and blood pressure and that these effects are mediated via the formation of angiotensin II.

Angiotensin II↗
PubMed1975

The relationship between sodium excretion and renin secretion by the perfused kidney.

The effect of altered tubular sodium reabsorption on renin secretion (RSR) was examined under conditions in which other factors influencing renin release could be controlled or excluded. To do this, isolated canine kidneys were perfused at constant pressure with blood circulating from donor animals. Volume expansion or hemorrhage of the donor dogs produced large changes in the animal's blood pressure, renal function, sodium excretion (UNaV), and RSR, but were without effect on renal hemodynamics, UNaV, or RSR in the perfused kidney. Hemodilution without volume expansion, resulted in hypotension, decreased UNaV and increased RSR in the donor dogs, and increased UNaV and suppressed RSR in the perfused kidney. These effects of hemodilution in the perfused kidney were partially reversed when plasma protein concentration was restored to control levels with hyperoncotic albumin, and, overall, there was a significant inverse relationship between electrolyte excretion and RSR. These results provide new evidence for the hypothesis that the rate at which sodium is delivered to the macula densa is an important determinant of the rate of renin secretion.

Animals↗
PubMed1975

Studies concerning the mechanism of suppression of renin secretion by clonidine.

Two series of experiments were performed in anesthetized dogs to test the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in the activity in the renal sympathetic nerves. In the first series, clonidine (1 mug/kg) was administered directly into the third ventricle of a group of dogs in which renal perfusion pressure was controlled by adjusting an aortic clamp. In these animals, clonidine produced hypotension and bradycardia and suppressed plasma renin activity to 39 percent of the control value. These changes in blood pressure and plasma renin activity were closely correlated. Intraventricular clonidine produced similar alterations in blood pressure and heart rate in another group of dogs in which renal perfusion pressure was not controlled, but failed to suppress plasma renin activity. In the second series of experiments, clonidine was administered intravenously in a dose of 30 mug/kg. Intravenous clonidine produced a transient hypertension followed by hypotension, decreased heart rate and suppressed plasma renin activity to 49 percent of the control value. Renal denervation reduced renin secretion and prevented the suppression of renin secretion produced by intravenous clonidine. Thus, these data are consistent with the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in renal sympathetic neural tone. This suppression may be overcome by large falls in renal perfusion pressure.

Animals↗
PubMed1972

An effect of extrarenal beta adrenergic stimulation on the release of renin.

The present study was undertaken to examine whether the beta adrenergic agonist, isoproterenol, increases plasma renin activity (PRA) by activation of intrarenal or extrarenal pathways. The effects of intravenous (i.v.) and renal arterial infusion of isoproterenol on PRA and renin secretion rate (RSR) were compared in anesthetized dogs. In 12 studies in 9 dogs i.v. infusion of isoproterenol (0.009-0.018 mug/kg per min) was associated with an increase in PRA from 14.7 to 35.7 ng/ml per 3 hr (P < 0.001). PRA decreased to 19.4 ng/ml per 3 hr (P < 0.001) after cessation of the infusion. In innervated kidneys RSR increased from 1640 to 5062 U/min (P < 0.02) and decreased to 2132 U/min after cessation of the infusion (P < 0.05). In denervated kidneys the control RSR was significantly lower (455 U/min) but still increased during i.v. infusion of isoproterenol to 2762 U/min (P < 0.001) and decreased to 935 U/min (P < 0.001) after the infusion was stopped. These changes in PRA and RSR were associated with an increase in cardiac output averaging 49% and a large decrease in total peripheral resistance. These effects of i.v. isoproterenol to increase RSR were not mediated by changes in renal perfusion pressure since this was held constant by adjusting a suprarenal aortic clamp. In addition, there were no changes in glomerular filtration rate, renal plasma flow, or electrolyte excretion in either denervated or innervated kidneys during i.v. infusion of isoproterenol, and the concentration of potassium in plasma was unchanged. Prior hypophysectomy abolished the antidiuretic effect of i.v. isoproterenol but did not prevent the effect on RSR. In contrast, renal arterial infusion of isoproterenol at the same dose had no apparent effect on PRA and RSR in seven studies in five dogs and also did not produce changes in cardiac output, peripheral resistance or renal hemodynamics. These results do not provide evidence for a role of intrarenal beta adrenergic receptors in the control of renin release and indicate that the effect of beta adrenergic stimulation with isoproterenol to increase the release of renin is mediated by an extrarenal mechanism. Since the effect of i.v. isoproterenol occurred in the absence of changes in plasma potassium concentration, renal perfusion pressure, glomerular filtration rate, renal plasma flow, and electrolyte excretion and was not abolished by renal denervation, the possibility must be considered that the effect on renin secretion is mediated by circulatory factors. The changes in systemic hemodynamics which occurred with i.v. but not renal arterial infusion of isoproterenol may be involved in the initiation of such a pathway.

Adrenergic beta-Agonists↗