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Biomedical subjects

I A Reid

Publications and source records attributed to I A Reid.

At least 19 recordsLinked to original sources
PubMed1979

Inhibition by alpha-adrenoceptor agonists of renin release in vitro.

A variety of alpha-adrenergic agonists encompassing a broad range of concentrations were used to investigate the existence and nature of a putative alpha-adrenergic mechanism inhibitory to renin release, which may operate at the level of the juxtaglomerular apparatus. For this purpose rat renal cortical tissue incubated in vitro was used. Concentrations of noradrenaline, adrenaline and methoxamine of 10(-6), 10(-5), 10(-4) and 10(-3) M caused significant dose-related inhibition of renin release. The inhibition of release by these doses was reversed completely by 10(-4) M phentolamine. In contrast, phenylephrine, oxymetazoline and clonidine did not inhibit renin release. The results support the concept of an alpha-adrenergic mechanism inhibitory to renin release and show that high concentrations of alpha-adrenergic agonist are required for its operation in vitro. The manner in which this inhibitory mechanism affects renin release under physiological circumstances remains to be demonstrated.

Adrenergic alpha-Agonists↗
PubMed1979

Partial purification of dog angiotensinogen.

Dog angiotensinogen was purified 450-fold from the plasma of nephrectomized dogs by a simple four-step procedure involving precipitation between 1.5 and 2.3 M ammonium sulfate, gel filtration on Sephadex G-150, ion-exchange chromatography on DE-52 cellulose, and affinity chromatography on Concanavalin A-Sepharose. The purity of the final preparation was over 50%. The preparation of dog angiotensinogen had an apparent molecular weight of 80,000 determined by gel filtration on Sephadex G-100. Kinetic studies indicated that the Km of the reaction of dog renin with partially purified dog angiotensinogen (1,840 pmol/ml) was similar to that for the reaction with angiotensinogen in diluted dog plasma (1,820 pmol/ml). Thus the purification procedures employed did not alter the affinity of dog renin for the Leu10-Leu11 bond of dog angiotensinogen. Because the concentration of angiotensinogen in dog plasma is about 700 pmol/ml, a first order reaction with respect to substrate is indicated in vivo.

Angiotensinogen↗
PubMed1979

Suppression of vasopressin secretion by clonidine: effect of alpha-adrenoceptor antagonists.

Studies were performed in anesthetized dogs to determine if the diuretic effect of clonidine results from inhibition of vasopressin secretion. Intravenous clonidine (30 microgram/kg) decreased plasma vasopressin concentration (as measured by RIA) from 10.9 +/- 1.5 to 5.0 +/- 1.1 ng/ml (P less than 0.01) in association with a transient increase in arterial blood pressure and a decrease in heart rate. Intravenous administration of two alpha-adrenoceptor antagonists, piperoxane and phentolamine, virtually abolished the pressor effect of clonidine but did not prevent the suppression of plasma vasopressin concentration. Clonidine decreased plasma vasopressin concentration from 11.9 +/- 3.1 to 3.3 +/- 1.0 pg/ml in the phentolamine-treated dogs (P less than 0.01) and from 18.1 +/- 4.5 to 12.4 +/- 3.6 pg/ml in the piperoxane-treated dogs (P less than 0.05). These results provide direct evidence that the diuretic effect of clonidine results from inhibition of the secretion of vasopressin. This inhibition does not appear to be a consequence of the pressor effect of the drug but may result from a direct action in the central nervous system.

Animals↗
PubMed1979

Localization of angiotensinogen in rat liver by immunocytochemistry.

Plasm angiotensinogen, the protein precursor of angiotensin, is produced by the liver. The present study investigated the location of angiotensinogen in sections of rat liver using the unlabeled peroxidase-antiperoxidase bridge technique of Sternberger. Specific reaction products of the antibody localization method were most pronounced in the cytoplasm of hepatocytes in the pericentral zone of the liver lobule. Controls, in which antibody was preabsorbed with angiotensinogen, did not form reaction product. The gradient of angiotensinogen observed within liver lobules resembled that demonstrated by metabolic zonation. The distribution of angiotensinogen differed from the scattered distributions found for other plasma proteins.

Angiotensinogen↗
PubMed1979

Mechanism of the dipsogenic action of tetradecapeptide renin substrate in dogs.

Dogs with chronically implanted third ventricular cannulae showed significant drinking responses to central injections of angiotensin II and tetradecapeptide renin substrate (TDP). The threshold dose for angiotensin II was 1 pmol and for TDP was 70 pmol. Although central injections of TDP led to drinking and appearance of angiotensin II in cerebrospinal fluid, renin substrate prepared from dog cerebrospinal fluid had no effect. The dipsogenic action of TDP was blocked by prior administration of converting enzyme inhibitor SQ20881 (P less than 0.01) but was not affected by either pepstatin or N-acetyl-pepstatin. Thus, converting enzyme acts directly on TDP to produce angiotensin I and then angiotensin II. The results of the present study do not provide evidence for the presence of an enzyme in the brain with renin-like activity.

Angiotensin II↗
PubMed1979

Effect of tetradecapeptide renin substrate on blood pressure, plasma renin activity, and vasopressin and adrenocorticotropin concentrations.

The effects of third ventricular injection of tetradecapeptide renin substrate (TDP) and natural renin substrate prepared from dog cerebrospinal fluid were compared in anesthetized dogs. Central injection of 350 pmol TDP caused a long lasting increase in arterial blood pressure, a reduction in PRA, and increases in plasma levels of vasopressin, and ACTH. In marked contrast, central administration of equimolar doses of natural renin substrate had no effect on these variables. Intracranial administration of the converting enzyme inhibitor SQ 20881 prevented the effects of central injection of TDP. Thus, TDP exerts its effects via conversion to angiotensin II and does not necessitate the postulation of the action of an enzyme with renin-like activity in the brain.

Adrenocorticotropic Hormone↗
PubMed1979

The brain renin-angiotensin system: a critical analysis.

The concept of a brain renin-angiotensin system originated with the observation that the components necessary for the formation of angiotensin II are present in the central nervous system. This observation has been confirmed and extended, and it is now frequently assumed that there is a functional brain renin-angiotensin system. However, careful analysis of the available evidence has revealed a number of significant problems. It appears that most of the renin-like activity measured in extracts of brain is due to the acid protease cathepsin D; this is unlikely to function as an angiotensin-forming enzyme in vivo. Experiments involving central administration of renin substrate have not provided convincing evidence for a significant renin-renin substrate interaction in vivo. Attempts to demonstrate the presence of angiotensin in the brain have been plagued with problems of specificity and it is still not clear if the peptide is actually present in the central nervous system. These problems do not rule out the possibility that there is a brain renin-angiotensin system, but more definitive evidence is required before it can be concluded that such a tensin system exists.

Angiotensin I↗
PubMed1979

Role of peripheral adrenoreceptors and vasopressin in the suppression of plasma renin activity by L-dopa in carbidopa-treated dogs.

When extracerebral dopa decarboxylase is inhibited by carbidopa, L-dopa lowers plasma renin activity (PRA). The present study was designed to determine whether this suppression of PRA is mediated by the sympathetic nerves, and to identify the peripheral adrenergic receptor types involved. All experiments were performed in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were minimized by means of a suprarenal aortic clamp. Neither alpha adrenoreceptor blockage with phenoxybenzamine nor beta adrenoreceptor blockade with propranolol was by itself sufficient to block the suppression of PRA by L-dopa with carbidopa. However, combined alpha and beta adrenoreceptor blockade lowered PRA and completely prevented any further suppression of PRA by L-dopa with carbidopa. It was also observed that phenoxybenzamine decreased PRA by 48% when administered to propranolol-treated animals. Taken together, these data indicate that L-dopa with carbidopa suppresses PRA by decreasing sympathetic nerve stimulation of both alpha and beta adrenoreceptors. Plasma vasopressin concnetration was significantly decreased by L-dopa with carbidopa both in the control group and in animals with combined alpha and beta adrenoreceptor blockade. Because plasma vasopressin levels decreased after L-dopa, vasopressin is unlikely to play a causative role in the suppression of PRA.

Animals↗
PubMed1978

Mechanism of the dipsogenic action of tetradecapeptide renin substrate.

The mechanism of the dipsogenic action of synthetic tetradecapeptide renin substrate (TDP) was studied in rats with chronically implanted lateral ventricular cannulae. All hormones and drugs were injected via the ventricular cannulae. The dipsogenic action of TDP was unaffected by the renin inhibitor pepstatin but was markedly reduced by the angiotensin converting enzyme inhibitor SQ 20881. Homogenates of rat brain readily formed angiotensin II from TDP in vitro and this was likewise unaffected by pepstatin but was reduced or abolished by SQ 20881 or by chelating agents. Natural renin substrate did not cause drinking and did not generate angiotensin II when incubated with brain homogenates. These results demonstrate that rat brain converting enzyme can generate angiotensin II from TDP and that this effect is responsible for the dipsogenic action of TDP.

Angiotensin II↗
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↗