PubMed Health⌕ Search

Biomedical subjects

I A Reid

Publications and source records attributed to I A Reid.

At least 109 records · Page 6Linked to original sources
PubMed1978

Effect of spinal cord transection on the endocrine and blood pressure responses to intravenous clonidine.

To determine whether the inhibitory effect of clonidine (CLON) on renin secretion is due in part to a direct action on the kidneys or due entirely to an action on the brain, the drug was administered intravenously in a dose of 30 microgram/kg to dogs in which the spinal cord had been transected in the cervical region. Renal perfusion pressure was held constant by adjusting a suprarenal aortic clamp. The decrease in plasma renin activity produced by CLON in dogs with intact spinal cords was abolished, and in 5 of 8 dogs tested, plasma renin activity rose. The decrease in blood pressure seen in control dogs was replaced by a prolonged pressor response. The ACTH response, as measured by plasma corticoids, and the growth hormone (GH) response were not significantly reduced. The data indicate that at least at this dose, the depressor response and the decrease in renin secretion produced by CLON are completely central in origin.

Adrenal Cortex Hormones↗
PubMed1978

Effect of norepinephrine on renin release and the cyclic AMP content of rat kidney slices: modification by sodium deficiency and alpha-adrenergic blockade.

The effect of L-norepinephrine (NE) on renin release by slices of kidney cortex from sodium-replete and sodium-deficient rats was studied in vitro. The rate of renin release by slices from sodium-deficient rats in the absence of added NE increased in proportion to the length of dietary sodium restriction and was significantly greater at all times than release by slices from sodium-replete animals. NE added to slices from the sodium-replete animals in concentrations ranging from 2 X 10(-9) to 2 X 10(-4)M caused a significant renin release only at a concentration of 2 X 10(-7)M. In contrast, the rate of renin release by slices from the sodium-deficient rats increased in a dose-related fashion when the NE concentration ranged from 2 X 10(-12) to 2 X 10(-7)M. NE in a concentration of 2 X 10(-5) had a lesser stimulatory effect, and 2 X 10(-4)M caused a significant inhibition of renin release. This inhibition was converted to stimulation by addition of the alpha-adrenergic blocking drug phentolamine. Phentolamine by itself was ineffective. The increases and decreases in renin release produced by NE were, in general, accompanied by increases and decreases in the cyclic AMP content of the slices. The changes in renin release were linear for 60 min, but the changes in cyclic AMP content were greater at 5 and 20 min than at 60 min. A dose-response relationship between the changes in renin release and cyclic AMP content was not observed. These data indicate that sodium deprivation enhances the sensitivity of the renin-secreting cells to catecholamine stimulation, and are consistent with the hypothesis that the increase in renin secretion produced by NE is mediated via cyclic AMP. The data also indicated that in high concentrations, NE exerts an inhibitory effect on renin release, and that this effect is mediated via stimulation of alpha-adrenergic receptors.

Animals↗
PubMed1978

Mechanism of suppression of renin secretion by clonidine in the dog.

The mechanism by which clonidine suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which renal perfusion pressure was controlled by means of an aortic clamp. Clonidine (30 microgram/kg, iv) lowered mean arterial pressure (MAP) from 124 +/- 8 to 104 +/- 4 mm Hg (P less than 0.01) and reduced plasma renin activity (PRA) to 32 +/- 4 percent of the control value (P less than 0.01) after 60 minutes. Ganglion blockade with pentolinium (3 mg/kg, im) decreased MAP from 148+/- 7 to 117 +/- 3 mm Hg (P less than 0.01) and reduced PRA to 55 +/- 13 percent of the control value (P less than 0.05) after 45 minutes. Pentolinium converted the hypotension produced by clonidine to hypertension (108 +/- 9 to 146 +/- 10 mm Hg at 60 minutes, P less than 0.05) and abolished the suppression of PRA (105 +/- 14 percent of control at 60 minutes, P less than 0.05). In a further series of experiments, the effects of oxymetazoline, an alpha-adrenergic receptor agonist which is closely related to clonidine but which does not cross the blood brain barrier, were studied. Oxymetazoline (10 microgram/kg, iv) increased MAP from 127 +/- 3 to 154 +/- 2 mm Hg (P less than 0.01) and elevated PRA TO 176 +/- 22 percent of the control value (P less than 0.02) after 30 minutes. A higher dose of oxymetazoline (30 microgram/kg) increased MAP from 129 +/- 10 to 161 +/- 9 mm Hg (P less than 0.05) and increased PRA to 256+/- 37 percent of control (P less than 0.05) after 30 minutes. Taken together, these data support the hypothesis that the inhibition of renin secretion by clonidine results from a centrally mediated decrease in sympathetic neural activity.

Animals↗
PubMed1978

Evidence that the effects of isoproterenol on water intake and vasopressin secretion are mediated by angiotensin.

The effect of isoproterenol (6 microgram/kg sc) on drinking, urine flow, and vasopressin secretion was examined in a group of trained dogs with chronically implanted third ventricular cannulae. Isoproterenol stimulated drinking in association with a reduction in urine flow and an increase in urine to plasma osmolality ratio. Plasma renin activity increased from 3.1 +/- 0.8 to 13.0 +/- 2.7 ng/ml/3 h and plasma vasopressin concentration increased from 11.3 +/- 1.3 to 40.3 +/- 12.5 pg/ml. The effect of isoproterenol was reexamined during an intracerebroventricular infusion of the angiotensin II antagonist, saralasin (0.02 microgram/kg/min). This treatment did not affect the isoproterenol-induced increase in plasma renin activity, but inhibited the drinking, antidiuresis, and increase in plasma vasopressin concentration. These data indicate that the effects of isoproterenol on drinking, urine flow, and vasopressin secretion are mediated via the renin-angiotensin system.

Angiotensin II↗
PubMed1978

Angiotensin II concentration in cerebrospinal fluid after intraventricular injection of angiotensinogen or renin.

To determine if the brain enzyme which has renin-like activity in vitro can form angiotensin in vivo, angiotensin II concentration in cerebrospinal fluid (CSF) was measured before and at various intervals after injection of partially purified renin substrate (angiotensinogen) into the third cerebral ventricle of anesthetized dogs. The injection increased CSF angiotensinogen concentration 3-fold, but despite this, CSF angiotensin II concentration, which was undetectable (less than 6.25 fmol/ml) before injection, did not change. Arterial blood pressure was also unchanged after the injection. In contrast, both CSF angiotensin II concentration and arterial pressure increased after an inventricular injection of renin. These results demonstrate that angiotensin II is formed centrally after administration of exogenous renin but not after injection of angiotensinogen. The results thus fail to demonstrate renin activity in the brain in vivo.

Angiotensin II↗
PubMed1977

Effect of angiotensin II and glucocorticoids on plasma angiotensinogen concentration in the dog.

The increase in plasma angiotensinogen concentration produced by angiotensin II infusion in the dog is accompanied by an increase in plasma corticosteroid concentration and is prevented by adrenalectomy. The present study was undertaken to test the possibility that the angiotensinogen response to angiotensin is mediated via an increase in glucocorticoid secretion. Infusion of angiotensin II (3-6 mug/h for 5 h) into the third cerebral ventricle of five dogs increased plasma corticosteroid concentration from 3.5+/-0.6 to 11.8+/-1.5 mug/dl (P less than 0.025) but did not increase plasma corticosteroid concentration from 2.7+/-0.4 to 7.8+/-1.5 mug/dl (P less than 0.05) but again failed to increase plasma angiotensinogen concentration. On the other hand, more prolonged glucocorticoid treatment with dexamethasone produced a significant increase in plasma angiotensinogen concentration within 24 h. Intravenous infusion of angiotensin II (50 mug/h for 5 h) in five acutely hypophysectomized dogs receiving a cortisol infusion caused only a small increase in plasma corticosteroid concentration (5.0+/-0.5 TO 6.9+/-0.6 mug/dl, P less than 0.02) but increased plasma angiotensinogen concentration from 967+/-122 to 1,358+/-204 ng/ml (P less than 0.02). These results indicate that although glucocorticoids can increase plasma angiotensinogen concentration, the angiotensinogen response to angiotensin II is not dependent on increased glucocorticoid secretion.

Adrenal Cortex Hormones↗
PubMed1977

An intrarenal effect of somatostatin on water excretion.

Intrarenal infusion of somatostatin in anesthetized dogs produced a prompt increase in urine flow in association with a decrease in urinary osmolality and an increase in free water clearance. These changes occurred in the absence of changes in arterial pressure, renal plasma flow, osmolar clearance, electrolyte excretion or cyclic AMP excretion. The diuretic effect occurred primarily in the infused kidney indicating a direct intrarenal action rather than suppression of vasopressin secretion. This diuretic action of somatostatin may result from inhibition of the action of vasopressin on the renal medulla but other possible mechanisms cannot be excluded.

Animals↗
PubMed1977

Role of central and peripheral mechanisms in the action of alpha-methyldopa on blood pressure and renin secretion.

The mechanism by which alpha-methyldopa lowers arterial pressure and suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were prevented by adjusting a suprarenal aortic clamp. After intravenous alpha-methyldopa (100 mg/kg) mean arterial pressure (MAP) decreased form 127+/-3 to a mean minimum of 107+/-4 mm Hg (P less than .01) and plasma renin activity (PRA) decreased from 20.6+/-4.8 to 10.9+/-1.7 ng/ml/3 hr (P less than .05). Blockade of peripheral dopa decarboxylase with intravenous carbidopa (20 mg/kg) significantly attenuated the hypotensive action of intravenous alpha-methyldopa but MAP still decreased from 145+/-6 to 130+/-5 mm Hg(P less than .001). Intravenous carbidopa completely abolished the fall in PRA produced by intravenous alpha-methyldopa (16.8+/-2.8 to 16.9+/-2.1 ng/ml/3 hr.) Intraventricular carbidopa (3 microng/kg/min) did not block the hypotensive (135+/-8 to 113+/-7 mm Hg, P less than .01) or renin-lowering effect (24.3+/-5 to 13.4+/-3.2 ng/ml/3 hr, P less than .01) of intravenous alpha-methyldopa (0.5 mg/kg decreased MAP from 118 +/- 5 to 104 +/- 5 mm Hg (P less than 0.001) but had no effect on PRA (23.4+/-6 TO 19.4+/-7 NG/ML/3 hr.) Intraventricular alpha-methylnorepinephrine (2 microng/kg) also decreased MAP from 127+/-5 to 112+/-3mm Hg (P less than .006) but again failed to significantly alter PRA (36.1+/-11.8 to 37.2+/-15 ng/ml/3 hr). These results indicate that there is both a central and peripheral component to the antihypertensive effect of alpha-methyldopa in the dog and that the suppression of renin secretion results from a peripheral action of the drug.

Animals↗
PubMed1977

Effect of L-dopa on plasma renin activity with and without inhibition of extracerebral dopa decarboxylase in dogs.

The aim of the present study was to investigate the possibility that catecholaminergic pathways within the central nervous system play a role in the control of renin secretion. Plasma renin activity (PRA) was measured after intravenous administration of L-dopa with and without prior inhibition of extracerebral dopa decarboxylase by carbidopa (MK-486) in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were minimized by means of a suprarenal aortic clamp. When L-dopa (20 mg/kg ) was administered intravenously without carbidopa. PRA and blood pressure increased. In contrast, administration of L-dopa (20 mg/kg i.v.) after blockade of extracerebral, but not cerebral dopa decarboxylase by intravenous carbidopa (20 mg/kg), produced significant decrease in both PRA and blood pressure. Larger doses of l-dopa (30-50) mg/kg i.v.) also lowered both PRA and blood presure in three carbidopa-treated animals, whereas a smaller dose of L-dopa (10 mg/kg i.v.) significantly lowered blood pressure but not PRA. In dogs with both kidneys acutely denervated, L-dopa (20 mg/kg i.v.) with carbidopa lowered arterial pressure but did not consistently alter PRA. These data suggest that catecholamines formed within the central nervous system can act to lower renin secretion as well as blood pressure.

Animals↗
PubMed1976

Pharmacological evidence for inhibition of ACTH secretion by a central adrenergic system in the dog.

To obtain more information about the transmitter involved in catecholaminergic inhibition of ACTH secretion, the site of this inhibition, and the receptors involved, the secretion of ACTH was studied in pentobarbital-anesthetized dogs that were surgically stressed and treated with drugs which modify central catecholaminergic transmission. The index of ACTH secretion was adrenal venous output of corticoid hormones. Intravenous L-dopa inhibited ACTH secretion, and this inhibition was not modified by blockade of peripheral decarboxylation of L-dopa with carbidopa. Intravenous or centrally administered clonidine inhibited stress-induced ACTH secretion, whereas centrally administered apomorphine did not. When given into the third ventricle, phenoxybenzamine (but not phentolamine) blocked the inhibitory effect of L-dopa and clonidine. Pimozide had no effect. L-propranolol caused a small but significant decrease in stress-induced ACTH secretion. Intraventricular procaine blocked the stress response. The data support the conclusion that the site of catecholaminergic inhibition of ACTH secretion is central, 'inside the blood-brain barrier', instead of the pituitary or the median eminence. They indicate that dopamine is not the mediator involved, and suggest that it is probably norepinephrine, although epinephrine is not ruled out. The receptor on which the released catecholamines act, presumably on the surface of the cells that secrete the hypothalamic hormone that regulates ACTH secretion, appears to be a type of alpha-adrenergic receptor.

Adrenocorticotropic Hormone↗
PubMed1976

Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs.

The role of brain catecholamines in the regulation of growth hormone secretion was investigated in pentobarbital-anesthetized dogs by using drugs which modify the function of adrenergic neurons and receptors. Intravenous administration of L-dopa produced a prompt, statistically significant increase in plasma growth hormone concentration. This response was not significantly reduced by blockade of peripheral dopa decarboxylase activity with carbidopa. Clonidine, an alpha-agonist which penetrates the brain, increased plasma growth hormone secretion. Norepinephrine, epinephrine, dopamine and isoproterenol, catecholamines which do not penetrate the blood-brain barrier, failed to affect plasma growth hormone concentration when administered intravenously. Apomorphine did not produce a statistically significant increase in plasma growth hormone concentration when administered directly into the the third ventricle, and pimozide failed to abolish the increase in plasma growth hormone produced by L-dopa. The increase in plasma growth hormone concentration produced by intravenous L-dopa and clonidine was prevented by administration of phentolamine or phenoxybenzamine directly into the third ventricle. The response to L-dopa was also abolished by intraventricular procaine. In dogs in which central beta-adrenergic blockade was produced by intraventricular L-propranolol, the growth hormone response to L-dopa was greater than it was in control dogs treated with intraventricular D-propranolol. The data indicate that in pentobarbital anesthetized dogs, the increase in growth hormone secretion produced by L-dopa is mediated by norepinephrine, rather than dopamine, that the site of action of the norepinephrine is central, above the median eminence and inside the 'blood-brain barrier', and that the norepinephrine acts via alpha-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1976

Effects of carotid occlusion and clonidine on renin secretion in anaesthetized dogs.

1. Sympathetic reflexes were activated by carotid occlusion in anaesthetized dogs in which changes in renal perfusion pressure were prevented. This produced a prompt and reversible increase in plasma renin activity. 2. Administration of clonidine decreased plasma renin activity, arterial pressure and heart rate and blocked the renin secretory and blood pressure responses to carotid occlusion. 3. These results support the hypothesis that the suppression of renin secretion by clonidine is a consequence of the decrease in sympathetic activity produced by this drug.

Animals↗
PubMed1976

Antidiuresis produced by injection of renin into the third cerebral ventricle of the dog.

The purpose of this study was to determine whether centrally administered renin stimulated vasopressin secretion. Vasopressin was not measured directly, but, instead, changes in urinary water excretion in anesthesized dogs undergoing a water excretion in anesthetized dogs undergoing a water diuresis were used as an index of changes in vasopressin secretion. Intraventricular injection of hog renin in a dose of 0.1 Goldblatt unit produced a marked decrease in urine flow which was associated with a decrease in free water clearance and an increase in urinary osmolatiy with no change in osmolar clearance. Sodium excretion increased significantly but there was no change in potassium excretion. These effects, which closely resemble those resulting from an increase in vasopressin secretion, were prevented by hypophysectomy. The antidiuretic effect clearly resulted from an action of renin in the central nervous system since renin had no effect on urine flow or osmolality when administered intravenously. Intraventricular administration of saralasin acetate, a specific antagonist of angiotensin II, completely blocked the effects of intraventricular renin indicating that these effects were mediated via the formation of angiotensin II. The data therefore indicate that there is an interaction between injected renin, brain angiotensinogen, and converting enzyme resulting in the formation of angiotensin II which stimulates the secretion of vasopressin. Additional studies are required to determine whether the brain renin-angiotensin system plays a physiological role in the regulation of a vasopressin secretion.

Animals↗
PubMed1976

Renin activity in dog brain: enzymological similarity to cathepsin D.

The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.

Animals↗