Mechanisms for aldosterone and spironolactone-induced positive inotropic actions in the rat heart.

Previously, we reported that aldosterone and spironolactone have inotropic effects in the isolated perfused heart. To address the mechanisms underlying these inotropic effects, we examined the effects of aldosterone and spironolactone on isolated cardiac myocyte shortening, intracellular calcium ([Ca+2]i), pHi, and calcium-dependent actinomyosin ATPase activity. Aldosterone significantly increased shortening in cardiac myocytes (8.

Localization of abnormal parathyroid tissue with use of technetium-99m-sestamibi.

Objective: To evaluate the efficacy of "double-phase" technetium-99m-sestamibi scanning in the localization of abnormal parathyroid tissue in patients with hyperparathyroidism.

Methods: We present a prospective review of patients with hyperparathyroidism seen at a university teaching hospital between June 1994 and May 1997. Twenty-four patients entered into the study underwent preoperative localization with double-phase technetium-99m-sestamibi.

Rapid effects of aldosterone and spironolactone in the isolated working rat heart.

Chronic administration of aldosterone promotes myocardial fibrosis in rats. The Randomized Aldactone Evaluation Study reported that the aldosterone antagonist spironolactone improved outcome in patients with congestive heart failure, suggesting a deleterious effect of aldosterone in the heart. Aldosterone has been shown to have rapid nongenomic effects in different tissues including the heart.

Regulation of the genes for 11beta-hydroxysteroid dehydrogenase type 1 and type 2 in the kidney of the Dahl rat.

Background: An isoenzyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), 11beta-HSD-2 confers aldosterone specificity on the mineralocorticoid receptor (MR) and is found collocated in renal cortical collecting duct cells with the MR. To investigate whether the salt sensitivity of the Dahl salt-sensitive (S) rat is due to 11beta-HSD deficiency, we measured 11beta-HSD-1 and 11beta-HSD-2 mRNA levels in the kidneys of Dahl-S and Dahl salt-resistant (R) rats. In addition, we studied the effects of gender, age and dietary sodium on expression of mRNA for the two isoforms.

11Beta-hydroxysteroid dehydrogenase in the Dahl rat.

Dahl salt sensitive (Dahl-S) rats develop hypertension soon after birth. The cause of the increased salt-sensitivity in the Dahl-S rat is unknown. The mineralocorticoid specificity of the kidney receptor is conferred by the activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD).

Reversal of the suppressed kidney renin level in the hypertensive transgenic rat TGR(mRen-2)27 by angiotensin converting enzyme inhibition.

The transgenic rat TGR(mRen-2)27 develops severe hypertension with high adrenal renin and low kidney renin. The mechanism of suppressed kidney renin in these animals is still unclear. We investigated the effect of the angiotensin converting enzyme (ACE) inhibitor, perindopril on the renin-angiotensin system in plasma and tissues (adrenal gland and kidney), and the effect of mouse renin antibody on plasma and tissue renin activity before and after perindopril administration.

Role of the tissue renin-angiotensin system in the action of angiotensin-converting enzyme inhibitors.

The mechanism of the blood pressure-lowering action of chronic administration of angiotensin-converting enzyme (ACE) inhibitors is still controversial. We investigated the effects of the ACE inhibitors, captopril and perindopril, on the renin-angiotensin system (RAS) in plasma and tissues (adrenal gland and kidney) in the rat. Captopril or perindopril was infused intraperitoneally into rats via a mini-osmotic pump for 6 days at a rate of 0.

Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-, and potassium-stimulated aldosterone secretion.

The zona glomerulosa cells of the adrenal gland have an intrinsic renin-angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells.

Acetaldehyde inhibits the anti-elastase activity of alpha 1-antitrypsin.

There are genetic and exogenous factors responsible for alpha 1-antitrypsin (alpha 1-AT) deficiency which may lead to cirrhosis of the liver and emphysema. The present study was initiated on a biochemical level in order to determine whether acetaldehyde, the major product of ethanol metabolism, is capable of influencing the physiological effect of alpha 1-AT upon elastase, an enzyme which is capable of inducing emphysema. The effects of acetaldehyde and ethanol upon elastase and alpha 1-AT were tested.

Hypertension in the transgenic rat TGR(mRen-2)27 may be due to enhanced kinetics of the reaction between mouse renin and rat angiotensinogen.

The transgenic rat TGR(mRen-2)27, in which the Ren-2 mouse renin gene is transfected into the genome of the rat, develops severe hypertension with high adrenal renin and low kidney renin. These animals express both mouse and rat renin. To investigate the cause of hypertension in the TGR rat, we compared the kinetics of mouse renin acting on mouse and rat angiotensinogens.

Effects of nephrectomy and adrenalectomy on the renin-angiotensin system of transgenic rats TGR(mRen2)27.

The transgenic rat TGR(mRen2) develops severe hypertension with high renin activity in the adrenal and low renin activity in the kidney. To clarify the role of the adrenal gland as a source of circulating renin in TGR rats, we investigated the effects of nephrectomy (NEPEX) and adrenalectomy (ADX) on the adrenal and plasma renin-angiotensin system. TGR rats had a high basal plasma renin concentration (PRC; 18.

Transforming growth factor-beta 1 inhibits aldosterone biosynthesis in cultured bovine zona glomerulosa cells.

Transforming growth factors (TGF beta s) are emerging as possible autocrine regulators of steroidogenesis in a variety of steroid hormone-producing cells. Our laboratory has recently shown that TGF beta 1 is a potent inhibitor of basal and ACTH- and (Bu)2cAMP-stimulated aldosterone production. In this study, we investigated the effects of TGF beta 1 on potassium- and angiotensin-II (A-II)-stimulated aldosterone and the mechanisms by which TGF beta 1 inhibits aldosterone biosynthesis.

Regulation of renin gene expression in rat adrenal zona glomerulosa cells.

Our previous studies indicated that the amount of renin present in cultured adrenal zona glomerulosa cells increased after stimulation with adrenocorticotropic hormone or potassium. In the present study, we investigated the effects of adrenocorticotropic hormone or potassium on renin gene expression in cultured rat adrenal zona glomerulosa cells. The amount of rat renin messenger RNA (mRNA) was measured by complementary DNA synthesis and the competitive polymerase chain reaction method.

Zonal distribution and regulation of adrenal renin in a transgenic model of hypertension in the rat.

The hypertensive transgenic rat [TGR (mRen-2)27] is a genetic model of hypertension in which transfection of the Ren-2 mouse renin gene into rats results in severe hypertension. These transgenic rats express a high level of renin in the adrenal gland, and the hypertension is ameliorated by treatment with angiotensin-converting enzyme inhibitors. In this study we investigated the distribution of adrenal renin in the TGR rat and examined the regulation of adrenal renin in a monolayer culture of adrenal cells.

Transforming growth factor-beta 1 inhibits aldosterone and stimulates adrenal renin in cultured bovine zona glomerulosa cells.

Transforming growth factors-beta (TFG beta s) are multifunctional peptides that affect proliferation, differentiation, and many other functions in a variety of cell types. In this study we examined the effect of TGF beta 1 on aldosterone and adrenal renin production using cultured bovine adrenal zona glomerulosa cells. Collagenase-dispersed zona glomerulosa cells were incubated in PFMR-4 medium containing 10% fetal calf serum for 72 h, and the medium was replaced with serum-free medium for the next 24 h.

Effect of atrial natriuretic peptide (8-33-Met ANP) in patients with hypertension.

In this pilot study we investigated the effects of a 4-h infusion of atrial natriuretic peptide (8-33 Met ANP) on hemodynamic, renal, and hormonal parameters in 12 patients with hypertension. Either 8-33 ANP in 5% mannitol (0.7 microgram/min [eight patients] and 1.

Regulation of the adrenal renin angiotensin system in cultured bovine zona glomerulosa cells: effect of catecholamines.

The renin-angiotensin system consists of two main enzymes, renin and angiotensin-converting enzyme, which lead to the formation of angiotensin-II. Angiotensin-II is a potent vasoconstrictor and stimulates the production of aldosterone. In this study we examined the effect of ACTH, potassium, (Bu)2cAMP (dbcAMP), and catecholamines on the adrenal renin-angiotensin system.

Effect of angiotensin II on renin production by rat adrenal glomerulosa cells in culture.

Angiotensin II (Ang II) inhibits renin secretion and production from the kidney, but the effect of Ang II on adrenal renin is not clear. Nephrectomy, via elevated plasma adrenocorticotropic hormone (ACTH) and potassium, is a strong stimulator of adrenal renin production in the rat. This stimulation is inhibited by the infusion of Ang II, suggesting a negative feedback between Ang II and adrenal renin.

Changes in cholesterol levels after coronary artery bypass surgery.

To determine the factors responsible for the dramatic fall in cholesterol levels after coronary artery bypass surgery (CABG), the authors reviewed, in a retrospective study, the cholesterol levels of 36 patients who underwent CABG surgery during 1987 and compared their levels with those of a control group of 30 patients who underwent cholecystectomies during the same time. In a prospective study, the authors measured the lipids and the hematocrit levels of 15 patients undergoing CABG surgery before the initiation of cardiopulmonary bypass, after 5 minutes of extracorporeal circulation (ECC), and at the end of ECC. In the CABG group, the plasma cholesterol level fell from 211 +/- 63 mg/dl (mean +/- SE) to 70 +/- 48 mg/dl (p less than 0.

Atrial natriuretic peptide inhibition of calcium ionophore A23187-stimulated aldosterone secretion in rat adrenal glomerulosa cells.

The effect of atrial natriuretic peptide (ANP) on calcium ionophore A23187-stimulated aldosterone secretion was investigated using collagenase-dispersed rat adrenal glomerulosa cell suspensions. A23187 treatment induced a dose-dependent stimulation of aldosterone secretion, exhibiting an EC50 of approximately 75 nM. In agreement with the presumed action of A23187 as a Ca2+ ionophore, stimulation was dependent on the extracellular Ca2+ concentration, being completely inhibited in nominally Ca(2+)-free medium.

Local generation of angiotensin II as a mechanism of aldosterone secretion in rat adrenal capsules.

Angiotensin-converting enzyme (ACE) is found in the adrenal gland, but the role of adrenal ACE in the formation of angiotensin II (AII) and subsequent stimulation of aldosterone is unclear. We examined the effect of adrenal ACE activity on aldosterone secretion by superfusing rat adrenal capsules with angiotensin I (AI) in the presence and absence of the ACE inhibitor, lisinopril. Angiotensin I (10 microM) stimulated aldosterone secretion from 914 +/- 41 to 1465 +/- 118 pg/min/capsule (P less than 0.

Guanabenz-induced inhibition of aldosterone secretion from isolated rat adrenal glomerulosa cells.

The authors examined the effects of the alpha 2-adrenergic agonist guanabenz and other alpha-adrenergic ligands on aldosterone secretion and cyclic nucleotide content in isolated rat adrenal glomerulosa cells. Guanabenz inhibited aldosterone secretion stimulated by potassium, angiotensin II (AII), and adrenocorticotropic hormone (ACTH), exhibiting IC50 values of 35 microM, 43 microM, and 58 microM for stimulation by 10 mM K+, 1 nM AII, and 10 pM ACTH, respectively. Guanabenz did not affect the cGMP content of purified adrenal glomerulosa cells but inhibited ACTH stimulation of cAMP accumulation.

Role of the adrenal renin-angiotensin system on adrenocorticotropic hormone- and potassium-stimulated aldosterone production by rat adrenal glomerulosa cells in monolayer culture.

The rat zona glomerulosa has a renin-angiotensin system that appears to function as an autocrine or paracrine system in the regulation of aldosterone production. To further investigate dynamic changes of production of renin and aldosterone in vitro we developed a primary monolayer culture of rat adrenal glomerulosa cells in serum-free medium. Collagenase-dispersed glomerulosa cells were incubated in PFMR-4 medium containing 10% fetal calf serum for 48 hours; the medium was then replaced with serum-free PFMR-4 medium.