Search PubMed⌕ Search

Biomedical subjects

S Oparil

Publications and source records attributed to S Oparil.

At least 325 records · Page 18Linked to original sources

Catecholamines, blood pressure, renin and myocardial function in the spontaneously hypertensive rat.

1. Neither nerve-growth-factor antiserum (NGFAS) administered subcutaneously nor 6-hydroxydopamine administered intraventricularly to immature spontaneously hypertensive rats (SHR) inhibited the development of the hypertensive syndrome. In contrast, NGFSA did not affect blood pressure in normotensive Kyoto/Wistar rats. 2. Peripheral vascular resistance was increased and cardiac index decreased in both NGFAS and 6-hydroxydopamine-treated SHR despite preservation of normal blood pressure. 3 NGFAS treatment did not influence the development of left ventricular hypertrophy in SHR, despite the lowering of blood pressure. In contrast, 6-hydroxydopamine caused an attenuation in the development of left ventricular hypertrophy. 4. Indices of left ventricular contractility were depressed by NGFAS treatment but not by 6-hydroxydopamine. 5. Plasma renin activity was unaffected by NGFAS treatment and increased by 6-hydroxydopamine.

Animals↗

Theoretical approaches to estimation of plasma renin activity: a review and some original observations.

Performance of accurrate, reproducible, and interpretable assays for plasma renin activity and other components of the renin/angiotensin system in the clinical setting requires a clear understanding of the various reactions in the renin/angiotensin cascade and the nature of their interactions. Plasma renin activity, the rate of angiotensin generations from plasma incubated in vitro, is the most commonly used clinical index of function in the renin/angiotensin system. Renin activity is measured by radioimmunoassay of angiotensin I generated in vitro under carefully controlled conditions. The value obtained for plasma renin activity depends on pH and duration of incubation and on the method used to protect the angiotensin I generated. We recommend incubation at neutral pH in buffered plasma for three hours in the presence of either ethylenediaminetetraacetate + 8-hydroxyquinolone + dimercaprol or ethylenediaminetetraacetate + phenylmethylsulfonylfluoride. Addition of a standard preparation of human renin to the plasma incubation step of the renin activity assay serves the dual purpose of permitting measurement of renin activity and furnishing an internal standard for comparison of assay procedures. The many variables among renin assay methods can be cancelled by referring to a common internal renin standard.

Angiotensin II↗

Oral-contraceptive-induced hypertension after adrenalectomy and hypophysectomy.

The cause of oral-contraceptive-induced hypertension in certain susceptible subjects is obscure. We describe a woman who was receiving replacement doses of fludrocortisone acetate after adrenalectomy and hypophysectomy who developed high blood pressure while ingesting an estrogen-containing oral contraceptive. Renin substrate level was increased, but renin activity was suppressed and unresponsive to tilting. The patient developed a markedly exaggerated natriuresis when infused with saline. Both blood pressure and her responses to infused sodium and tilting normalized after discontinuance of the oral contraceptive medication. In this adrenalectomized patient, the estrogenic component of the pill acting synergistically with a fixed ("nonsuppressible") replacement dose of mineralocorticoid seems to have caused a volume-related hypertension.

Adenoma, Chromophobe↗

Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity.

1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.

Adult↗

Fate of labeled angiotensin II microinfused into individual nephrons in the rat.

14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder

Angiotensin II↗

Prevention of hypertension in the SH rat: effects of differential central catecholamine depletion.

Six-hydroxydopamine (6-OHDA) was administered intraventricularly to 6-week-old male spontaneously hypertensive (SH) rats of the Okomoto strain and to normotensive rats of the Kyoto-Wistar strain. In addition, bilateral lateral tegmental lesions were placed in 35-40-day-old SH rats to interrupt ascending noradrenergic pathways. SH rats treated with 6-OHDA did not develop hypertension and had lower heart rates than control rats. Blood pressure and heart rate of Kyoto-Wistar animals were unaffected by the drug treatment. 6-OHDA produced widespread depletion of norepinephrine throughout the CNS of both SH and Kyoto-Wistar rats. Bilateral lateral tegmental lesions interrupted the dorsal noradrenergic bundle and depleted forebrain norepinephrine. These lesions did not prevent the development of hypertension and led to an increased heart rate. It is concluded that 6-OHDA does not produce its effect through a nonspecific lowering of blood pressure, but rather, that it interferes with the expression of the hypertensive syndrome. The lack of effect seen following depletion of forebrain norepinephrine as the result of interruption of the dorsal noradrenergic bundle indicates that the fibers destroyed by this lesion are not essential for the development of genetically determined hypertension.

Age Factors↗