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.

Angiotensin II and aldosterone regulation.

The circulating renin-angiotensin system is a major regulator of the secretion of the adrenocortical hormone, aldosterone. This renin-angiotensin aldosterone system is important in the control of salt and water balance and blood pressure. This review describes the historical background leading to the discovery of aldosterone in the 1950s and the recognition in the 1960s that angiotensin II was involved in its control.

Renin-angiotensin system in the adrenal.

Extrarenal renin has been found in a number of tissues. All the components of the renin-angiotensin system have been identified in the adrenal cortex. Adrenal renin has been found in many animal species, including the human, but most of the studies have been carried out in the rat.

Detection and control of hypertension in the population: the United States experience.

Trends in prevalence, awareness, treatment, and control of hypertension in the adult US population are reported. The data are from the National Health and Nutrition Examination Surveys (NHANES), carried out in four separate surveys, the last being NHANES III, 1988-1991. The age-adjusted prevalence of hypertension at > or = 160/95 mm Hg declined from 20% to 14%, and at > 140/90 mm Hg it declined from 36.

Secondary hypertension: evaluation and treatment.

Most patients with hypertension in the United States have essential (primary) hypertension (95%), the cause of which is unknown. The remaining 5% of adults with hypertension have the secondary form of hypertension, the cause and pathophysiologic process of which are known. Internists and other primary care physicians refer to this as treatable or curable hypertension, because the hypertension can be managed or even controlled with medications.

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.

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.

The intrarenal renin-angiotensin system.

The standard concept of the renin-angiotensin system is that renin is secreted by the juxtaglomerular cells of the kidney into the circulation, where it cleaves angiotensin to release angiotensin I. The angiotensin I is converted to angiotensin II by a converting enzyme located on the plasma membrane of the endothelial cell. The released angiotensin II binds to receptors on target cells to initiate a series of intracellular actions that result in a specific cell function.

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.

Adrenal renin: regulation and function.

Extrarenal renin has been identified in a variety of tissues. All of the components of the renin-angiotensin system have been detected in some organs, including the adrenal gland. A number of hypotheses have been expressed regarding the physiological function of these extrarenal renin systems, but no specific function has been clearly identified.