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Biomedical subjects

M I Phillips

Publications and source records attributed to M I Phillips.

At least 181 records · Page 10Linked to original sources
PubMed1979

Anteroventral third ventricle lesions reduce antidiuretic responses to angiotensin II.

Ablation of anteroventral third ventricle (AV3V) periventricular tissue renders animals temporarily adipsic with no compensatory change in urine volume or concentration. The present experiment was designed to determine whether lesions of the AV3V region attenuate vasopressin (AVP) release in response to intraventricular (ivt) injections of angiotensin II (AII), hypertonic NaCl, and phenylephrine during the adipsic period. Blood pressure, urine conductance, and urine flow rate were monitored in awake, unrestrained animals during a continuous intravenous hydrating infusion. Changes in blood pressure and urine parameters were recorded following ivt injections of 100 ng AII, 500 ng AII, 1 microliter 3% NaCl, and 50 microgram phenylephrine. In addition, a radioimmunoassay (RIA) measured AVP following 500 ng AII ivt in lesioned and nonlesioned animals. Antidiuretic and pressor responses to ivt AII were attenuated after AV3V lesions. In addition, RIA analysis showed a significantly smaller concentration of AVP in lesioned animals following AII injections. These data suggest that the AV3V region is important for AVP release in response to central AII and osmotic stimuli.

Angiotensin II↗
PubMed1979

Osmosensitivity of rat third ventricle and interactions with angiotensin.

Injections of hyperosmotic solutions (1- to 5-microliter injections of NaCl or sucrose solutions ranging in osmolarity from 0.34 to 0.90 osmol/l) into the anteroventral third ventricle (AV3V) of rats resulted in short latency drinking antidiuretic, and pressor responses. AV3V injections or infusions of combined angiotensin-hyperosmotic NaCl solution did not result in drinking greater than the sum of drinking to angiotensin and hyperosmotic NaCl separately administered. Differences in water versus saline drinking fluid preferences provided a behavioral dissociation of angiotensin and hyperosmotic sensitive neural mechanisms. Comparison of AV3V and lateral preoptic injection sites provided an additional separation since angiotensin was equally effective at both sites whereas osmotic stimulation was more effective at the AV3V site. AV3V lesions have previously been reported to abolish drinking, antidiuretic, and pressor responses to angiotensin and hyperosmotic stimulation. The data reported here provide additional evidence that angiotensin and hyperosmotic stimuli may both act on tissue surrounding AV3V but suggest that the neural substrates for these stimuli are not identical.

Angiotensin II↗
PubMed1979

Central effects of angiotensin II in water and saline loaded rats.

In unanesthetized water-loaded rats, intracerebroventricular (IVT) angiotensin II (AII) injections produce centrally mediated pressor effects and antidiuresis. Experiments were performed to evaluate the role of antidiuretic hormone (ADH) release versus neurogenic mechanisms in the antidiuretic responses to central AII median eminence lesions used to block ADH release abolish antidiuretic effects but only attenuated pressor responses to IVT AII infusions. Pretreatment with an intravenous infusion of ADH antibody had a similar effect. Central administration of AII in water and saline-loaded rats produced no change in effective renal plasma flow or glomerular filtration rate, Natriuretic and kaliuretic responses to IVT AII injections were similar to those observed to intravenous ADH infusions. These data are consistent with the suggestion that antidiuresis and osmotic excretion observed after IVT AII injections in the rats are the result of ADH release, and that neurogenic mechanisms play a major role in the blood pressure but not in the antidiuretic responses.

Angiotensin II↗
PubMed1978

Effects of central and peripheral angiotensin blockade in hypertensive rats.

The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.

Angiotensin II↗
PubMed1978

Effects of intraventricular angiotensin II mediated by the sympathetic nervous system.

Central effects of angiotensin II were studied in rats treated with adrenalectomy, chemical sympathectomy with intravenous 6-hydroxydopamine, or a combination of both. Unrestrained, unanesthetized rats were compared before and after one of the three treatments to determine water drinking and blood pressure responses to intracerebroventricular (ivt) injections of 50 and 500 ng angiotensin II (AII). Adrenalectomy alone did not alter either drinking or pressor response to AIIivt. Peripheral sympathectomy alone resulted in a prolonged latency for pressor response but did not significantly alter drinking response to AIIivt. Results obtained by combined treatment were not significantly different from results obtained by sympathectomy alone. There remained a pressor response to AIIivt after combined treatment. The adrenals do not appear to be involved in mediating pressor response to AIIivt. Furthermore, sympathetic neural activation alone causes the early pressor response to AIIivt. Finally, some other factor(s) in addition to sympathetic neural activation must contribute to the pressor response to AIIivt.

Adrenalectomy↗
PubMed1978

Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade.

The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.

Animals↗
PubMed1978

Central cholinergic and noradrenergic stimulation in spontaneously hypertensive rats.

In order to test the integrity of central receptors, spontaneously hypertensive rats (SHR) of the Okamoto strain and weight-matched control rats of the Wistar Kyoto (WKY) strain were given intracerebroventricular (i.vt.) injections of carbachol and norepinephrine. The rats, in an unanesthetized, unrestrained state, were tested for drinking, antidiuretic and pressor responses. Antidiuretic hormone release was determined by using water loaded, diuresing rats as their own antidiuretic hormone bioassay. Blood pressure was measured directly from a femoral artery catheter. Drinking responses to i.vt. carbachol and antidiuretic responses to i.vt. carbachol and norepinephrine infusions were not different between SHR and WKY while pressor responses were potentiated in SHR. The potentiated pressor responses to central carbachol and norepinephrine injections were the result of increased vascular responsiveness to the antidiuretic hormone released by these drugs. A second, neurally mediated, factor was also apparent to i.vt. carbachol injections. This additional factor could be increased sympathetic outflow to central drug stimulation, increased vascular reactivity to sympathetic outflow, decreased baroreflex responses or a combination of the above.

Animals↗
PubMed1977

Independent receptors for pressor and drinking responses to central injections of angiotensin II and carbachol.

Angiotensin II and carbachol when injected in the brain ventricles of the rat produce similar responses of an increase in blood pressure and drinking behavior. The question of whether these effects are produced by independent receptors or via a cholinergic circuit is debatable for the drinking behavior and evidence is lacking for the blood pressure effect. We have used a chronic rat preparation for recording blood pressure and drinking at the same time during intraventricular injections (i.v.t.) of both angiotensin and carbachol and i.v.t. or intravenous infusions of appropriate antagonists. The results show that drinking and blood pressure response to angiotensin II can be blocked by P113 (500 ng 1.v.t.) an angiotensin antagonist; they are not blocked by atropine (10 mug i.v.t.) a cholinergic antagonist; carbachol effects, however, are not blocked by P113, but are totally blocked by atropine (10 mug i.v.t.), At high doses of atropine there is inhibition of both agents but this probably represents a general inhibition. The hormone and cholinomimetic administered together interact and both are inhibited by adrenergic stimulation. We conclude from these experiments that angiotensin and carbachol act upon independent receptors in the brain to produce blood pressure and drinking responses but at some point they share common, central effector pathways.

Angiotensin II↗
PubMed1977

Central angiotensin II-induced responses in spontaneously hypertensive rats.

The brain isorenin angiotensin system has been implicated in the development of spontaneous hypertension by several investigators. The experiments reported here were designed to test the responsiveness of unanesthetized spontaneous hypertensive (SH) rats to intracerebroventricular angiotensin II injections compared to Wistar-Kyoto (WK) normotensive controls. The results indicate that there is no difference between SH and WK animals in drinking responses or antidiuretic hormone release to central angiotensin II injections; however, an increased pressor responsiveness to intraventricular angiotensin II in SH as compared to WK was observed. The results of intravenous infusions of pressor substances in these experiments and reports by other investigators suggest that the increased blood pressure effects to central angiotensin are due to three possible factors: 1) increased vascular responsiveness of SH to vasoconstrictor substances in general, 2) increased vascular sensitivity of SH rats to sympathetic outflow, and 3) decreased baroreceptor reflexes to acute increases in blood pressure. We suggest that the brain isorenin-angiotensin system may be involved in spontaneous hypertension by increased production of angiotensin II or by activation of a potentiated sympathetic system, but not by a generalized increased sensitivity of brain receptors to central angiotensin.

Angiotensin II↗