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Biomedical subjects

T A Kotchen

Publications and source records attributed to T A Kotchen.

At least 127 records · Page 7Linked to original sources
PubMed1979

Hypertension and aldosterone overproduction without renin suppression in Cushing's syndrome from an adrenal adenoma.

Adrenal steroids and compenents of the renin-angiotensin system were measured before and after adrenalectomy in a woman with Cushing's syndrome and hypertension from a functioning adrenocortical adenoma. Aldosterone, deoxycorticosterone and cortisol were produced in excess by the adenoma, and were measured in tumor tissue. High plasma renin substrate concentrations, and normal basal and furosemide-stimulated plasma renin activities and plasma renin concentrations which were present before surgery, decreased after adrenalectomy, and the hypertension diminished. The inappropriately normal levels of renin and potassium in this patient, despite autonomous aldosterone overproduction, suggest an ineffective mineralocorticoid action of aldosterone, possibly from interaction with her other adenoma-produced steroids. The decrease in components of the renin-angiotensin system suggests a partial renin-dependence of her hypertension.

Adenoma↗
PubMed1979

Effects of furosemide on renal venous plasma renin activity.

A control study comparing plasma renin activity (PRA) in the renal vein and the inferior vena cava was performed in 50 hypertensive patients before and after furosemide stimulation. In unilateral renal arterial stenosis, furosemide was found to stimulate secretion by the normal kidney more than by the ischemic kidney. When a renal venin PRA ratio of 1.5 or higher was used for lateralization, rates of 30% false-negatives and 60% false-positive resulted. Acute stimulation of renin by furosemide does not increase the predictive value of renal venous renin measurements and may actually result in a higher percentage of false-negatives.

False Negative Reactions↗
PubMed1979

Stimulation of renin by acute selective chloride depletion in the rat.

To determine whether acute chloride depletion per se stimulates renin, we produced selective chloride depletion without sodium depletion in rats by peritoneal dialysis (PD) against 0.15 M NaHCO3 or 0.15 M NaNO3. Control rats were dialyzed against 0.15 M NaCl. Plasma renin activity (PRA) was measured before (PRA1) and 105 minutes after (PRA2) PD. Plasma volume was expanded after PD by infusion of salt-free albumin and was measured immediately after PRA2 by [131I]albumin. In experiment 1, rats were prepared on a normal diet. PRA2 (7.0 +/- 1.0 ng/ml per hr, mean +/- SEM) was increased (P less than 0.05) over PRA1 (4.7 +/- 0.7 ng/ml per hr) in Cl-depleted but not in control rats (PRA1 = 5.3 +/- 0.7, PRA2 = 6.1 +/- 0.7, P = NS). In experiment 2, to produce greater chloride depletion, all rats were prepared for 2 weeks on a low salt diet. PRA2 (47 +/- 5 ng/ml per hr) was increased as compared to PRA1 (24 +/- 2 ng/ml per hr, P less than 0.005) in the Cl-depleted group but not in the control group (PRA1 = 24 +/- 3, PRA2 = 27 +/- 6 ng/ml per hr, P = NS). Serum potassium and final plasma volume were slightly but not significantly lower than controls in these Cl-depleted rats. To exclude an additive effect of these two stimuli for renin, in experiment 2a we infused chloride-depleted rats with three times as much albumin as controls and with KHCO3, 100 mEq/liter. Despite volume expansion and potassium loading, PRA2 (41 +/- 6 ng/ml per hr) was significantly elevated as compared to PRA1 (25 +/- 4 ng/ml per hr, P less than 0.01). Since acute metabolic alkalosis also was present in all Cl-depleted renin-stimulated rats, an additional group (2b) was dialyzed against 0.15 M NaNO3; final plasma arterial pH (7.43) was not different from controls (7.42). Nevertheless, PRA2 levels again were higher (36 +/- 6 ng/ml per hr, P less than 0.05) as compared to PRA1 (23 +/- 4 ng/ml per hr). In all experiments, arterial blood pressure, glomerular filtration rate, and filtered sodium load were not different. Free water reabsorption was lower in Cl-depleted than in control rats. We conclude that acute selective chloride depletion per se is a potent stimulus for renin release.

Alkalosis↗
PubMed1979

Peripheral beta-receptor responsiveness in patients with essential hypertension.

Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among "normal-renin" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure.

Adult↗
PubMed1979

Hyperprolactinemia--a review of recent clinical advances.

Since the radioimmunoassay for serum prolactin became available eight years ago, prolactin has become a hormone of considerable clinical interest. An elevated serum prolactin concentration is the most frequent hormone marker for pituitary tumors. Secreted in excess, prolactin causes dysfunction of the hypothalamic-pituitary axis, the gonads, and the adrenal cortex. In women, menstrual disturbances, galactorrhea, infertility, and hirsutism result. Impotence, oligospermia, and decreased libido are common in men. These metabolic abnormalities attributed to prolactin excess are corrected when prolactin concentrations are lowered by either medical or surgical therapy. The availability of effective therapy mandates early recognition and proper management of the patient with hyperprolactinemia.

Bromocriptine↗
PubMed1979

Antithyroid drugs and radioactive iodine. Fifteen years' experience with Graves' disease.

The population for this study included 186 patients who were treated between 1962 and 1977 for diffuse toxic goiter. Patients were divided into two groups according to the primary mode of therapy, which was either thioamides or sodium iodide I 131. Of 96 patients who were treated with primary drug therapy, only 16% experienced a prolonged remission (more than two years) of hyperthyroidism. Except for a greater likelihood of remission among patients with mild hyperthyroidism, no other clinical features of Graves' disease were predictive of the long-term response to drug therapy. Among the 90 patients who received primary sodium iodide I 131 therapy, those who were pretreated with thioamides required a higher total dose to achieve a cure (13.8 mCi vs 9.6 mCi) and had a lower initial incidence of hypothyroidism (54% vs 73%).

Adolescent↗
PubMed1978

In vitro and in vivo inhibition of renin by fatty acids.

Circulating neutral lipids inhibit the in vitro renin reaction. To identify the inhibitor(s), free fatty acids were added to human renin and homologous substrate. Capric, lauric, palmitoleic, linoleic, and arachidonic acids each inhibited the rate of angiotensin I production in vitro (P less than 0.01). Inhibition by polysaturated fatty acids (linoleic and arachidonic) was less (P less than 0.01) after catalytic hydrogenation of the double bonds. To evaluate an in vivo effect of renin inhibition intra-arterial blood pressure responses to infusions of renin and angiotensin II (5.0 microgram) were measured in anephric rats (n = 6) before and after infusion of linoleic acid (10 mg iv). Mean increase of blood pressure to angiotensin II before (75 mmHg +/- 9) and after (90 +/- 12) linoleic acid did not differ (P greater than 0.05). However, the pressor response to renin after linoleic acid (18 +/- 3) was less (P less than 0.00)) than that before (102 +/- 13). In summary, several fatty acids inhibit the in vitro renin reaction, and in part inhibition is dependent on unsaturation. Linoleic acid also inhibits the in vivo pressor response to renin. These results suggest that fatty acids may modify the measurement of plasma renin activity and may also affect angiotensin production in vivo.

Angiotensin I↗
PubMed1978

Importance of chloride for acute inhibition of renin by sodium chloride.

To evaluate the contribution of chloride to acute renin inhibition by sodium chloride, plasma renin activity (PRA) was measured before and after peripheral venous infusion of NaCl, NaHCO3, NaBr, NaNO3, lysine monohydrochloride, or lysine glutamate in NaCl-deprived rats. In contrast to controls and animals infused with other sodium salts, PRA decreased (P less than 0.01) after infusion with NaCl [from 28.3 +/- 2.8 to 13.3 +/- 1.8 ng/ml per h (SE)] and NaBr (from 40.6 +/- 6.2 to 21.8 +/- 3.9 ng/ml per h), and renal tubular halide reabsorption increased (P less than 0.05). Arterial pressure, plasma volume, inulin clearance, net sodium balance, serum Na+ and K+, and pH were not different among sodium-loaded groups. PRA was also suppressed (P less than 0.01) by infusion with lysine monohydrochloride (from 51.6 +/- 5.4 to 32.4 +/- 5.1 ng/ml per h) but not with lysine glutamate. These results suggest that inhibition of renin by sodium is dependent on an intrarenal effect of chloride. During infusion with sodium salts which suppressed renin, negative free water clearance (TcH2O) increased, whereas infusion with sodium salts that did not inhibit renin resulted in either no change or decreased TcH2O. The association of renin inhibition and increased TcH2O indirectly supports the hypothesis that renin suppression by chloride is related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle.

Amino Acids↗
PubMed1978

Failure of chronic sodium chloride loading to protect against norepinephrine-induced acute renal failure in dogs.

We previously have shown that chronic sodium chloride (NaCl) loading protects against HgCl2-induced acute renal failure (ARF) in dogs. To determine whether NaCl loading protects against an ischemic model of ARF, unilateral oliguric renal failure was produced by the infusion of norepinephrine (NE) into the renal artery of both saline-expanded (SE) and water-drinking (WD) dogs (n = 7). The renal renin content (30 U/g kidney) of SE dogs was suppressed (P less than 0.001) compared to that of WD dogs (132 +/- 18). Forty-eight hours after infusion of NE (1.5 microgram/kg per min X 100 min), inulin clearances from the infused kidney of SE (6 ml/min +/- 2) and WD dogs (7 +/- 2) did not differ; in both groups, respective clearances from the noninfused kidney (43 ml/min +/- 3) and (36 +/- 5) also did not differ from each other. The present fall in renal blood flow to the infused kidney 48 hours after NE in SE (44%) and WD dogs (38%) did not differ. Because of failure to demonstrate protection, a lower dose of NE (0.75 microgram/kg per min X 40 min) was infused into SE and WD animals (n = 6). Forty-eight hours after low dose NE, inulin clearances of the infused kidney of SE (17 ml/min +/- 5) and WD dogs (17 +/- 4) did not differ. Respective clearances in the noninfused kidney of SE (46 ml/min +/- 6) and WD dogs (35 +/- 4) did not differ. Therefore, despite suppression of renal renin content, NaCl loading failed to protect against this ischemic model of ARF. In conclusion, unlike HgCl2-induced ARF, it is unlikely that the renin angiotensin system contributes to the pathogenesis of this ischemic model of ARF.

Acute Kidney Injury↗
PubMed1977

Diuretic therapies in low renin and normal renin essential hypertension.

This study was designed to compare the effectiveness of spironolactone, hydrochlorothiazide, and combined spironolactone-hydrochlorothiazide therapy in patients with low renin and those with normal renin essential hypertension. Patients with low renin hypertension had a greater hypotensive response to each regimen (p less than 0.001). Low renin patients responded equally to both spironolactone and to hydrochlorothiazide, and in low renin but not in normal renin patients reduction of blood pressure correlated with weight loss. These results suggest that a volume factor, not specifically related to increased mineralocorticoid production, contributes to the pathogenesis of low renin essential hypertension.

Adult↗
PubMed1977

Effects of calcium on renin and aldosterone in the rat.

CaCl2 suppresses the plasma renin activity (PRA) response to Na+ deprivation in the rat. The purpose of the present study is:1) to determine if the effect of Ca2+ on PRA is modified by the anion delivered with Ca2+, and 2) to evaluate the effect of Ca2+ loading on aldosterone production. PRA and in vitro aldosterone production by adrenal quarters were measured after a 7-day balance study. On a low Na+ diet, PRA of animals drinking 1% CaCl2 (13.1 ng/ml per h +/- 1.3 SE), but not of animals drinking 1% calcium gluconate, was suppressed (P less than 0.05) compared to that of water-drinking controls (20.9 ng/ml per h +/- 2.1 SE). Aldosterone production of calcium gluconate and CaCl2-loaded animals was greater than that of controls (P less than 0.01). K+ balance of CaCl2 and calcium gluconate-drinking animals was more positive than that of controls (P less than 0.05). In conclusion, inhibition of PRA by CaCl2 but not by calcium gluconate indicates that the effect of Ca2+ on PRA is modified by the accompanying anion. Both CaCl2 and calcium gluconate stimulate aldosterone production, independent of changes in PRA, possibly due to an effect of Ca2+ on K+ balance.

Adrenal Glands↗
PubMed1977

Renal venous plasma renin reactivity in clinical and experimental renovascular hypertension: renin reactivity in renovascular hypertension.

Plasma renin reactivity (PRR) is the in vitro rate of angiotensin generation after addition of exogenous renin to plasma. The purpose of the present study is to compare measurements of PRR in venous effluent from the involved and uninvolved kidneys in both experimental and clinical renovascular hypertension. A two-kidney model of experimental hypertension was created by placing an ameroid resin constrictor around one renal artery in each of seven dogs. Plasma renin activity (PRA) in venous plasma from the involved kidney increased (p less than 0.001); comparing PRA in venous effluent from the stenotic and nonstenotic kidneys, the PRA ratio also increased ( p less than 0.005). Renal venous PRR did not change on either side after occlusion of the renal artery (p greater than 0.1), and the renal venous PRR ratio did not differ from the mean control ratio of 1.0 +/- 1 SE (p greater than 0.1). Similarly, in 9 patients with renovascular hypertension, mean PRR in venous plasma from the two kidneys did not differ (p greater than 0.8). These results suggest that measurement of renal venous PRR is not helpful in confirming a diagnosis of renovascular hypertension.

Angiotensin I↗
PubMed1977

Inhibition of the in vitro renin reaction by circulating neutral lipids.

We have previously reported that the addition of plasma from normotensive human subjects to renin-renin substrate inhibits the in vitro rate of angiotensin generation. The purpose of the present study was to determine whether a renin-inhibiting factor could be identified in human plasma. Neutral lipids and phospholipids were extracted from plasma of seven normotensive control subjects. During 30-, 60-, and 180-minute incubations, neutral lipids inhibited the reaction between human renin and homologous renin substrate (P less than 0.01). Phospholipids did not affect the rate of angiotensin generation (P less than 0.05). The neutral lipid extract was further separated on silica gel chromatographic plates, and several fractions inhibited renin (P less than 0.01) Addition of each of six synthetic neutral lipids to renin-renin substrate did not affect the rate of angiotensin generation. In conclusion, several neutral lipid fractions extracted from human plasma inhibit the in vitro renin reaction.

Angiotensin I↗