PubMed Health⌕ Search

Biomedical subjects

T A Kotchen

Publications and source records attributed to T A Kotchen.

At least 91 records · Page 5Linked to original sources
PubMed1985

Renin secretion and loop of Henle chloride reabsorption in the adrenalectomized rat.

Renin release is increased in the adrenalectomized rat and is not inhibited by sodium chloride administration. The purpose of this study was to determine whether increased renin release is related to impaired absorptive chloride transport in the loop of Henle. Chloride transport in the loop was measured before and after acute saline infusion in three groups of rats: 1) saline-drinking adrenalectomized rats (Adx); 2) saline-drinking dexamethasone-treated adrenalectomized rats (Dex); and 3) water-drinking sham-operated controls. Unrelated to differences of arterial pressure, glomerular filtration rate, or net sodium chloride balance, chloride reabsorption in the loop of Henle of Adx [836 +/- 172 peq/min (SE)] was less (P less than 0.01) than in controls (1,646 +/- 353) and Dex (1,377 +/- 318) before saline infusion. After saline infusion, chloride delivery to the loop increased (P less than 0.05) in all three groups. However, loop chloride reabsorption increased (P less than 0.01) only in controls and Dex but not in Adx. Before saline infusion, plasma renin concentration (PRC) of Adx (350 +/- 108 U/ml) was greater (P less than 0.01) than that in controls (56 +/- 6) or Dex (108 +/- 36); sodium chloride infusion failed to inhibit PRC in Adx, whereas PRC was suppressed (P less than 0.01) by saline in Dex and controls. Thus stimulation of renin release in adrenalectomized animals was associated with decreased absorptive chloride transport in the loop of Henle. Dexamethasone normalized loop function and renin responsiveness to sodium chloride.

Absorption↗
PubMed1985

Distribution of renin activity and angiotensinogen in rat brain. Effects of dietary sodium chloride intake on brain renin.

The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2 +/- 0.6 to 54.4 +/- 19.7 fmol/mg protein per h (mean of 7 +/- SD), with the highest amounts in pineal, pituitary, and pons-medulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCl-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P less than 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands.

Angiotensinogen↗
PubMed1985

Identification of renin inhibitors in normal and uremic plasma.

The enzymatic activity of renin is increased in plasma of patients with renal failure, possibly because of the deficiency of a renin inhibitor. Our study was undertaken to identify renin inhibitors and to compare their activities in plasma of 10 normal humans and 10 patients with renal failure. In vitro, both human renal renin and purified mouse submaxillary renin were inhibited by intact plasma and by a high molecular weight (greater than 65,000 daltons) and a lower molecular weight (55,000 daltons) plasma fraction (HMF and LMF, respectively) obtained by Sephadex chromatography. Most plasma proteins were recovered in HMF, and LMF also contained a small amount of protein; however, renin inhibition by HMF and LMF was not dependent on the presence of intact protein. HMF extracted from normal and uremic plasma inhibited renin to a comparable extent. However, LMF from uremic plasma inhibited renin to a lesser extent (p less than 0.01) than LMF from normal plasma. HMF-free plasma of normal subjects contained a specific renin-inhibiting neutral lipid component that was absent in uremic plasma. Thus, circulating renin inhibitors may contribute to the overall activity of the renin-angiotensin system, and increased enzymatic activity of renin in plasma of patients with renal failure may be related to the deficiency of a normally occurring neutral lipid renin inhibitor.

Adult↗
PubMed1984

Salt-sensitive hypertension: contribution of chloride.

The effect of the anion associated with sodium loading on the development of hypertension in the Dahl salt-sensitive rat was determined. For 5 weeks rats were fed a diet containing normal or high concentrations of sodium chloride or high concentrations of sodium provided as a mixture of sodium bicarbonate, phosphate, and amino acids. After 1 week on these diets and until the end of the study the rats receiving high concentrations of sodium chloride had higher systolic blood pressures than the rats in the other two groups. There were no statistically significant group differences in plasma volume, arterial pH, or plasma concentrations of Na+, K+, Cl-, Ca2+, or creatinine, or in renomedullary prostaglandin E2 production. Compared to the animals receiving normal concentrations of sodium chloride, those receiving high concentrations of sodium chloride or amino acids showed decreased plasma renin activity and plasma aldosterone concentrations. Thus, the anion ingested with sodium alters the development and severity of hypertension in the Dahl salt-sensitive rat.

Animals↗
PubMed1984

Prazosin as initial antihypertensive therapy: correlates of sympathetic function.

Abnormal sympathetic function has been proposed as a factor in the development of essential hypertension. If this is the case, prazosin hydrochloride, which works by a selective, peripheral, antisympathetic effect--postsynaptic alpha blockade--may have an advantage over other antihypertensive agents. In this study, blood pressure response and measures of sympathetic and baroreflex function were followed in 13 hypertensive patients. Prazosin alone significantly reduced standing and sitting diastolic blood pressures without affecting pulse rates, plasma catecholamines or baroreflex slopes in all patients. The addition of a thiazide diuretic in persons who did not achieve goal blood pressure on prazosin alone was generally successful in reducing blood pressure to desired levels, and increased both plasma renin activity and aldosterone concentrations. No significant relation was apparent between specific characteristics of sympathetic function and response to prazosin as initial therapy, although patients responding tended to have initially higher plasma norepinephrine concentrations.

Adult↗
PubMed1984

Addison's disease with adrenal enlargement on computed tomographic scanning. Report on two cases of tuberculosis and review of the literature.

Two patients with Addison's disease related to urogenital tuberculosis had enlargement of one or both adrenal glands detected with computed tomographic scanning. Review of reports of adrenal size on computed tomographic examination suggests that adrenal enlargement in the presence of Addison's disease demands further investigation about the cause of the adrenal insufficiency.

Addison Disease↗
PubMed1984

Enzymatic activity of renin in plasma of normal and uraemic subjects.

Plasma renin reactivity (PRR) is the rate of angiotensin I production after addition of renin to plasma, minus endogenous renin activity. PRR is increased in plasma of patients with renal failure compared with that of normal subjects. The present study was carried out to determine if increased PRR in uraemic plasma is related to differences of endogenous active or inactive renin, endogenous renin substrate, or pH of the incubation in vitro. PRR in plasma of ten uraemic patients was greater (P less than 0.02) than that in plasma of ten normal subjects in incubations carried out at pH 7.4 and 5.7. Increased PRR was not accounted for by differences of endogenous active and inactive renin activity. After addition of renin, renin concentration (measured by direct radioimmunoassay) did not differ in normal and uraemic plasma. Renin substrate concentration, measured both indirectly and by direct radioimmunoassay, also did not differ in normal and uraemic plasma. Increased PRR in uraemic plasma is not related to alterations of renin or renin substrate concentrations. These observations are consistent with our earlier hypothesis that there is a deficiency of a renin inhibitor in uraemic plasma.

Angiotensinogen↗
PubMed1984

[Effects of potassium on renin and aldosterone].

The renin-aldosterone system contributes to the regulation of arterial pressure and to the maintenance of sodium and potassium balance. Alterations in plasma potassium concentration have opposite and independent effects on renin secretion by the kidney and on aldosterone secretion by the adrenal gland. Renin secretion tends to be inhibited by hyperkalemia and stimulated by potassium depletion. In contrast, increases of plasma potassium directly stimulate aldosterone secretion. This effect of potassium on aldosterone serves as a protective mechanism against the development of hyperkalemia. Conversely, hypokalemia inhibits aldosterone production. Small changes in plasma potassium have a greater effect on aldosterone than on renin secretion. In patients with essential hypertension, diuretic induced alterations in serum potassium concentrations may affect both renin and aldosterone secretion. We have observed that therapy with a thiazide diuretic results in a reduction of serum potassium and a greater increase in renin activity than therapy with the potassium-retaining diuretic, spironolactone, despite comparable natriuretic responses with both drugs. Conversely spironolactone therapy is associated with a greater increase in aldosterone production. The greater effect of thiazides on renin activity and the greater effect of spironolactone on aldosterone production may be related to the thiazide induced reduction of serum potassium and the spironolactone induced increases of serum potassium.

Aldosterone↗
PubMed1983

Blood pressure related echocardiographic changes in adolescents and young adults.

In 1973, standardized blood pressure measurements were obtained in 837 high school students in Bourbon County, Kentucky, a rural county with a high prevalence of individuals with systemic hypertension. In 1978, follow-up measurements of blood pressure were performed in selected individuals who were in the high, intermediate, and low ranges of the initial sex-specific blood pressure distributions. Relative rank order of initial blood pressure measurements over the five-year period was maintained. The results of this population-based study provided an opportunity to evaluate the cardiac status in young adults with relatively high blood pressures maintained over five years. Standard m-mode echocardiographic examinations were, therefore, performed over five years. Standard m-mode echocardiographic examinations were, therefore, performed at the time of follow-up. In individuals in the low and intermediate ranges for systolic blood pressure, indices of ventricular hypertrophy were directly correlated with blood pressure level. Among individuals with higher values for systolic blood pressure, after adjusting for the effects of relative body size, indices of ventricular hypertrophy were not significantly different from those noted in the intermediate group. Indices of cardiac performance and estimated left ventricular systolic wall stress were, however, significantly elevated in this "high" blood pressure group. Early in the course of systemic hypertension increased wall stress, rather than hypertrophy, appears to be the primary cardiac manifestation of elevated systolic blood pressure.

Adolescent↗
PubMed1983

Clonidine in patients with diabetes and mild hypertension.

Clonidine has been reported to adversely affect glucose tolerance in experimental animals and normal man. We assessed its short- and long-term effects in 10 patients with both mild hypertension and diabetes mellitus. Patients were studied before and 10 wk after treatment with 0.1 mg clonidine twice daily, which induced reductions in blood pressure (from 148 +/- 5/93 +/- 2 mm Hg sitting, to 125 +/- 4/80 +/- 2) and control of hypertension in all patients. Clonidine increased the glycemic response to intravenous glucose (incremental glucose AUC from 161 +/- 13 to 184 +/- 14) but did not significantly change long-term diabetic control as assessed by weekly fasting serum glucose, glycosylated hemoglobin, and 24-hr urinary glucose excretions before and after treatment. We conclude that low-dose clonidine controlled blood pressure and impaired the response to an acute glucose challenge in midly hypertensive, type II diabetic patients but did not adversely affect diabetic control over 10 wk.

Adult↗
PubMed1983

Effects of NaCl on renin and aldosterone responses to potassium depletion.

We have previously suggested that renin secretion is inversely related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle. Potassium depletion inhibits chloride transport at this site in the nephron. Consequently, we studied the effects of varying sodium and chloride intakes on the renin and aldosterone responses to potassium depletion. Potassium depletion prevented suppression of plasma renin activity (PRA) by dietary NaCl loading and augmented the PRA response to NaCl deprivation. PRA was stimulated (P less than 0.01) by selective chloride (without sodium) deprivation, and potassium depletion did not augment this response. Potassium depletion did not interfere with suppression of PRA by albumin-induced volume expansion. Plasma aldosterone was suppressed by potassium depletion, and the effect of potassium depletion on aldosterone was augmented by NaCl deprivation. In conclusion, the magnitude of PRA stimulation and aldosterone suppression by potassium depletion is modulated by dietary NaCl intake. The results are consistent with the hypothesis that potassium depletion stimulates renin release by inhibiting chloride transport in the loop of Henle.

Aldosterone↗
PubMed1983

Effects of verapamil on renin and aldosterone in the dog and rat.

The purpose of this study was to evaluate the effects of calcium channel blockade on renin secretion and plasma aldosterone. Verapamil infusion (0.004 mg X kg-1 X min-1) into the renal artery of uninephrectomized dogs with an intact kidney resulted in significant increases (P less than 0.05) in renal blood flow, creatinine clearance, and the excreted fractions of Na+ and Cl-; renin secretion decreased (P less than 0.05) and plasma aldosterone did not change. Conversely, renal arterial infusion of verapamil in dogs with nonfiltering, denervated, papaverine-treated kidneys resulted in no change in renal blood flow and a significant increase (P less than 0.05) in renin secretion. In the rat, compared with untreated control animals, dietary verapamil (12.5 mg X kg-1 X day-1) did not effect plasma renin activity but significantly suppressed plasma aldosterone (P less than 0.001) in animals on NaCl-restricted [14.7 +/- 5.4 vs. 41.6 +/- 7.8 ng/dl (SE)] and NaCl-free [103.7 +/- 7.5 vs. 156.7 +/- 18.7 ng/dl (SE)] diets. In addition, verapamil suppressed (P less than 0.0003) plasma corticosterone [16.1 +/- 5.4 vs. 52.8 +/- 7.1 microgram/dl (SE)]. Thus, acute but not chronic verapamil administration stimulates renin release in the nonfiltering kidney, and chronic verapamil inhibits adrenal mineralocorticoid and glucocorticoid secretion. The disparate effects of verapamil on renin secretion from intact and nonfiltering kidneys may be due to actions of the Ca2+ channel blocker on renal hemodynamic and/or renal tubular mechanisms in the intact kidney that mask a direct effect of verapamil on renin-secreting cells.

Aldosterone↗
PubMed1983

Effect of adrenalectomy on renin release in the rat.

The purpose of this study was to evaluate the mechanism of increased renin secretion in the adrenalectomized (Adx) rat. Plasma renin concentration (PRC) responses to acute infusion of 0.9% NaCl (5% of body weight) were compared in three groups of rats: Adx, Adx rats treated with dexamethasone (Adx + Dex), and sham controls. During the 7 days after adrenalectomy and before acute infusion. Adx animals drank 0.9% NaCl; sham animals drank water. Despite a more positive sodium balance over the 7 days, preinfusion PRC was higher in Adx than in the other two groups (P less than 0.01) and did not decrease with NaCl infusion [31.2 +/- 9.6 (+/-SE) U/30 min to 30.4 +/- 9.5]. PRC was suppressed by NaCl infusion in Adx + Dex (10.2 +/- 2.4 to 4.1 +/- 1.2) and sham controls (9.7 +/- 0.9 to 2.6 +/- 0.5). In separate groups of animals, PRC decreased (P less than 0.01) in response to volume expansion with 25% albumin (1% of body weight) in both Adx (42.6 +/- 8.9 to 23.1 +/- 6.1) and sham controls (10.2 +/- 1.2 to 2.1 +/- 0.7). These results are consistent with the hypothesis that altered responsiveness to NaCl, in the absence of volume contraction, contributes to increased renin release in adrenal insufficiency. Glucocorticoid replacement restored renin responsiveness to NaCl.

Adrenal Glands↗
PubMed1983

Suppression of adrenal mineralocorticoid production in prehypertensive young adult men.

We assessed the renin-aldosterone axis in response to treadmill exercise and adrenal steroidogenesis after graded ACTH infusions in two groups, each composed of nine young adult men from Bourbon County, Kentucky, from the upper and lower deciles of the blood pressure distribution. Those from the upper decile with relatively higher blood pressures, termed prehypertensive, had significantly lower plasma aldosterone and 18-hydroxycorticosterone concentrations after graded ACTH than those with relatively lower pressures, and had significantly lower urinary potassium excretions. Renin and aldosterone responses to exercise were also significantly blunted in the prehypertensive subjects. No differences were found in plasma cortisol, deoxycortisol, deoxycorticosterone, corticosterone, or dehydroepiandrosterone sulfate, although dehydroepiandrosterone was higher at one infusion rate in prehypertensives. These findings suggest that the adrenal mineralocorticoid pathway and the renin-aldosterone axis are suppressed in prehypertensive young males perhaps as an appropriate feedback response to their higher blood pressures.

18-Hydroxycorticosterone↗
PubMed1983

Effects of intravenous and oral verapamil upon pressor and adrenal steroidogenic responses in normal man.

Slow channel calcium antagonists inhibit in vitro both vascular smooth muscle contraction and adrenal steroidogenesis. We assessed the effects of one of these drugs, verapamil, upon pressor responses and increments in plasma steroid concentrations to adrenal trophic factors in normal volunteers. Given acutely iv, verapamil in amounts sufficient to produce plasma concentrations of approximately 200 ng/ml significantly blunted the pressor action of angiotensin II in six normal subjects but did not alter increments in plasma aldosterone or cortisol in response to either angiotensin or ACTH compared to paired control studies. When verapamil was given orally (120 mg three times daily for 5 days), the plasma concentrations were equivalent to those after iv administration of the drug in six other volunteers, and verapamil again significantly blunted pressor responses to angiotensin II and norepinephrine. Oral verapamil also blunted the increments in plasma aldosterone to angiotensin and cortisol to ACTH, but did not alter the aldosterone response to ACTH. We conclude that verapamil given either acutely or chronically impaired the action of pressor hormones by a nonspecific action on vascular smooth muscle. When given for a sustained period of time, verapamil also impaired to a moderate degree adrenal steroidogenesis to two trophic factors, suggesting that its adrenal effect is time dependent.

Adrenocorticotropic Hormone↗
PubMed1983

Effect of chloride on renin and blood pressure responses to sodium chloride.

Both the inhibition of renin release by sodium chloride and salt-sensitive hypertension have been attributed to sodium. We evaluated the contribution of chloride to these responses to sodium chloride. In the Sprague-Dawley rat, acute and chronic administration of sodium salts other than sodium chloride failed to suppress plasma renin activity, whereas renin was inhibited by both sodium chloride and by selective chloride (without sodium) loading. Plasma renin activity was stimulated by selective chloride depletion. Similarly, in humans, plasma renin activity was suppressed by sodium chloride but not by sodium bicarbonate infusion. In a preliminary study in the Dahl salt-sensitive rat, in contrast to sodium chloride loading, sodium bicarbonate loading failed to produce hypertension. Thus, both the renin and possibly the blood pressure responses to sodium chloride are dependent on chloride.

Adult↗