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Biomedical subjects

R H Freeman

Publications and source records attributed to R H Freeman.

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

The use of angiotensin II blockade to study adrenal steroid secretion.

In the dog, the renin--angiotensin system appears to be a primary control mechanism for aldosterone secretion since angiotensin II blockade decreased aldosterone production to undetectable levels. Angiotensin II blockade also decreased cortisol secretion strikingly in dogs with thoracic caval constriction, a finding which suggests the presence of an angiotensin II receptor in the two inner zones of adrenal cortex. An important incidental finding after angiotensin II blockade in both sodium-depleted dogs and dogs with thoracic caval constriction was the striking drop in arterial pressure. It is suggested that angiotensin II acts on the peripheral arterioles to provide an important compensatory mechanism and, thereby, maintain arterial pressure in these low cardiac output states. In the rat, both the nonapeptide converting enzyme inhibitor and [Sar1, Ala8]-angiotensin II produced a marked decrease in aldosterone secretion in hypophysectomized, sodium-depleted animals. Both synthetic angiotensin II and its heptapeptide fragment produced striking increases in aldosterone secretion when the obscuring effect of ACTH was excluded in the rat. These findings provide evidence that the renin--angiotensin system is an important control mechanism for aldosterone biosynthesis in the rat.

Adrenal Glands↗
PubMed1975

High-output heart failure in the dog: systemic and intrarenal role of angiotensin II.

Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water secondary to hypersecretion of both renin and aldosterone. The present study was undertaken to evaluate the systemic and intrarenal arteriolar action of angiotensin II (AII) in dogs with HOF and to provide additional information about the role of AII in low-output states. The intravenous infusion of a specific AII antagonist, [Sar1, Ala8]AII (6 mug/kg min-1), into conscious dogs with HOF decreased the mean arterial pressure (AP) from 101 +/- 7 to 83 +/- 7 mmHg (P less than 0.01) after 45 min of infusion. Intrarenal arterial infusion of the AII antagonist (0.2 and 2.0 mug/kg min-1) into anesthetized dogs with HOF also decreased AP and produced a marked increase in renal blood flow (RBF) with no changes in either creatinine clearance or sodium excretion. Similar results were obtained during the intrarenal infusion of the antagonist into sodium-depleted dogs and dogs with thoracic vena caval constriction, but not in normal dogs. The data demonstrate an important role for AII in the regulation of AP and RBF in high- and low-output states.

Angiotensin II↗
PubMed1975

Des-1-Asp-angiotensin II. Possible intrarenal role in homeostasis in the dog.

The relative effects of des-a-Asp-angiotensin 3I and angiotensin II on renal function, including renin secretion, were investigated in normal and sodium-depleted dogs. Intrarenal arterial infusion of the heptapeptide fragment into normal dogs at a rate which was calculated to increase blood levels by only 7 ng/100 ml decreased renal blood flow from 254 +/- 9 ml/min to 220 +/- 12 and 219 +/- 12 ml/min (P less than 0.01 for both values) after 10 and 30 minutes of infusion, respectively; renin secretion decreased from 502 +/- 214 ng/min to 253 +/- 109 and 180 +/- 53 ng/min (P less than 0.05 for both values). Infusion of angiotensin II at the same rate decreased renal blood flow from 251 +/- 26 ml/min to 224 +/- 22 and 220 +/- 16 ml/min (P less than 0.01 and 0.025, respectively) and decreased renin secretion from 374 +/- 25 ng/min to 166 +/- 76 and 131 +/- 37 ng/min (P less than 0.025 for both values). Neither peptide significantly changed mean arterial blood pressure, creatinine clearance, or excreted sodium in these dogs. Infusion of des-1-Asp-angiotensin II into sodium-depleted dogs decreased renin secretion from 1094 +/- 211 ng/min to 768 +/- 132 and 499 +/- 31 ng/min (P less than 0.025 for both values) after 10 and 30 minutes of infusion. Angiotensin II infusion decreased renin secretion from 1102 +/- 134 to 495 +/- 235 and 502 +/- 129 ng/min in these dogs (P less than 0.05 and 0.025, respectively). Neither peptide significantly altered renal blood flow, arterial blood pressure, creatinine clearance, or excreted sodium in the sodium-depleted dogs. The data demonstrated that these two peptides have similar effects on the renin secretory mechanism and the vascular receptor at the level of the renal arterioles.

Angiotensin II↗
PubMed1975

Control of aldosterone secretion in the spontaneously hypertensive rat.

Adrenal secretion rates of aldosterone, corticosterone, and deoxycorticosterone were studied sequentially in the spontaneously hypertensive rat and the normotensive Kyoto Wistar rat. Steroid secretion was studied at three different ages: 7-8, 11-13, and 22-25 weeks. Also, peripheral plasma levels of aldosterone and plasma renin activity were determined in both the spontaneously hypertensive and the normotensive rats at 7-8 weeks of age. Aldosterone secretion was elevated markedly in dexamethasone-morphine-treated spontaneously hypertensive rats at both 7-8 and 11-13 weeks of age but was not significantly different from control in 22-25-week-old spontaneously hypertensive rats. No statistically significant differences in corticosterone or deoxycorticosterone secretion rates were observed between the spontaneously hypertensive rats and the normotensive Kyoto Wistar controls; however, the data suggested that dexamethasone did not suppress adrenocorticotropic hormone in the 7-8- and 11-13-week-old spontaneously hypertensive rats to the same extent that it did in the normotensive Kyoto Wistar rats. Therefore, aldosterone secretion was reexamined in acutely hypophysectomized 7-8-week-old rats to eliminate completely the influence of the anterior pituitary; no differences in aldosterone, corticosterone, or deoxycorticosterone secretion rates were observed between hypophysectomized spontaneously hypertensive rats and normotensive Kyoto Wistar rats. Moreover, aldosterone secretion in the hypophysectomized 7-8-week-old spontaneously hypertensive rats was reduced markedly compared with that in the intact 7-8-week old spontaneously hypertensive rats, thus confirming the importance of the pituitary in these animals. Determinations of peripheral plasma aldosterone concentration and plasma renin activity in unstressed 7-8-week-old spontaneously hypertensive and normotensive rats revealed that both parameters were depressed significantly in the spontaneously hypertensive rats. Thus, the present data indicate that the renin-angiotensin-aldosterone system is suppressed in the spontaneously hypertensive rat but do not suggest that the system is critically involved in the hypertensive process in these animals

Adrenal Glands↗
PubMed1975

Arterial pressure regulation during hemorrhage: homeostatic role of angiotensin II.

The role of the renin-angiotensin system in the maintenance of arterial pressure following hemorrhage was studied in conscious dogs. Hemorrhage (20 ml/kg body wt) decreased the mean arterial pressure, but compensatory mechanisms partially restored the arterial pressure toward normal. Plasma renin activity increased more than twofold following hemorrhage. To evaluate the role of endogenous angiotensin II in this compensatory response, a specific competitive antagonist of angiotensin II, 1-sarcosine-8-alanine-angiotensin II, was infused intravenously at 6.0 mug/kg min-1 for 30 min; the mean posthemorrhage arterial pressure decreased from 102 plus or minus 7 mmHg to 80 plus or minus 6 mmHg after 15 and 30 min of analog infusion (P less than 0.01 for both values). After a recovery period of 60 min, arterial pressure returned to pre-infusion levels. These results suggest that angiotensin II plays an important role in the short-term maintenance of arterial pressure following hemorrhage in the conscious animal.

Angiotensin II↗
PubMed1975

DES-ASP1--angiotensin II: possible role in mediating responses of the renin-angiotensin system.

In dexamethasone-treated dogs, both antiogensin II and its heptapeptide fragment (des-asp1-angiotensin II) stimulated the secretion of the adrenal steroids aldosterone, corticosterone, and cortisol. Further, there was no statistically significant difference in the steroidogenic potency of the two peptides. An interesting incidental finding was the decrease in PRA with both peptides, again with no demonstrable difference in the magnitude of the responses. The present data are consistent with the hypothesis that the heptapeptide mediates responses produced by the renin-angiotensin system in both the adrenals and the kidneys.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Renal hemodynamic response to intrarenal infusion of calcitonin gene-related peptide in dogs.

The renal hemodynamic and excretory effects of intrarenal infusions of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in normal sodium replete dogs (Group 1, n = 6), in sodium replete dogs pretreated with indomethacin (Group 2, n = 6), and in sodium deplete dogs (Group 3, n = 5). In all groups of anesthetized dogs beta-hCGRP was infused at 5 and 10 ng.kg-1.min-1 for 50 min periods each. In the sodium replete group, beta-hCGRP infusions strikingly increased renal blood flow, but this response was markedly attenuated in the other 2 groups. During beta-hCGRP infusions, the clearance of creatinine also increased significantly in the sodium replete and deplete groups, but not in the indomethacin pretreated animals. No consistent changes in urinary sodium excretion or plasma renin activity were observed with beta-hCGRP infusions in any of the 3 groups of dogs. These results indicate that beta-hCGRP is a potent renal vasodilator and can increase renal blood flow and glomerular filtration. The data also suggest that the renal hemodynamic actions of beta-hCGRP are partially mediated by renal prostaglandins, and that the vasodilatory effects of beta-hCGRP may be antagonized by high circulating levels of endogenous angiotensin II in sodium-volume depletion. Finally, beta-hCGRP does not appear to have significant actions on urinary sodium excretion or plasma renin activity under the experimental conditions of the present study.

Animals↗
PubMedDate not supplied

Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs.

The systemic cardiovascular and renal effects of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. beta-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p greater than 0.05) in either group during low dose infusion of beta-hCGRP, but infusion of beta-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140 +/- 4 to 116 +/- 6 mmHg (p less than 0.05) in the hypertensive dogs (n = 4) and from 100 +/- 4 to 78 +/- 3 mmHg (p less than 0.05) in the normotensive dogs (n = 4). Heart rates increased significantly during infusion of beta-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p less than 0.05) in the two groups at both the low and high doses of beta-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p less than 0.05) in 1K-1C hypertensive dogs at the high rate of beta-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p less than 0.05) in both groups with the low dose infusion of beta-hCGRP but further increases were elicited only in the normotensive dogs in response to the elevation in the beta-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p less than 0.05) above control levels during the maximum hypotensive response to beta-hCGRP infusion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMedDate not supplied

Circadian changes in plasma renin activity and plasma aldosterone concentration in two-kidney hypertension rats.

Circadian changes in plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in normal and hypertensive rats were determined by measurements at 8 a.m., 4 p.m. and 12 midnight (MN). For the normals, PRA and PAC were highest at 4 p.m. Animals made hypertensive by constriction one renal artery with the other kidney intact were studied after 4, 5, 7 and 10 weeks; the clear-cut circadian rhythm for PRA in normals had disappeared but for PAC the circadian rhythm was present in the 4-, 5- and 10-week groups. Both PRA and PAC were elevated in all four hypertensive groups compared with the normal controls and there was a highly significant correlation between PRA and PAC. The 4 p.m. peak value for PAC was much higher in relation to the 8 a.m. and 12 MN values values in the hypertensive animals than in the normals. Sodium balance studies failed to demonstrate any appreciable differences among the groups. When the hypertensive animals were divided into two groups on the basis of the level of hypertension, the rats with moderate hypertension showed an average elevation in PRA which was significant in only the 4- and 7-week groups whereas PRA was elevated in all four groups with severe hypertension. Thus, the present data help to define the activity of the renin-angiotensin-aldosterone system in two-kidney, one clip hypertension in the rat.

Aldosterone↗
PubMedDate not supplied

Hypertension produced by sodium depletion and unilateral nephrectomy: a new experimental model.

Unilateral nephrectomy of sodium-restricted male Sprague-Dawley rats produced a sustained elevation in systolic blood pressure (SBP) that was reversed by sodium repletion. A chronic intraperitoneal infuson of SQ14,225 prevented the development of hypertension in sodium-deplete unilaterally nephrectomized rats. Sodium depletion of two-kidney rats increased SBP to a lesser extent, while unilateral nephrectomy of sodium replete animals had no effect. These results provide evidence for a new model of experimental hypertension in the rat and emphasize the importance of a renal component, as demonstrated by unilateral nephrectomy, in the maintenance of normal pressure-volume relationships.

Animals↗