Atrial natriuretic peptide kinetic studies in patients with cardiac dysfunction.

Three studies were performed: (1) a controlled investigation of alpha-human atrial natriuretic peptide (alpha-hANP) total body production and metabolic clearance rates using a bolus infusion technique (controls, patients 1 to 6); (2) a study of alpha-hANP kinetics in cardiac dysfunction patients using a constant infusion method (patients 7 to 14); and (3) a right heart catheterization study to determine the amount of alpha-hANP released into the circulation at the level of the right heart, estimated by the step-up in alpha-hANP concentration between the superior and inferior vena cava and the pulmonary artery, in the patients with left ventricular dysfunction. Baseline venous plasma alpha-hANP was 27.3 +/- 16.

Demonstration of processing and recycling of biologically active V1 vasopressin receptors in vascular smooth muscle.

The present study examines the binding and postbinding cellular processing and recycling of the V1 arginine vasopressin (AVP) receptor in cultured vascular smooth muscle cells (VSMCs). The surface binding of AVP to VSMCs was temperature dependent and reached equilibrium within 60 min at 4 degrees C. Displacement studies with unlabeled AVP or a specific V1 AVP antagonist revealed a single class of V1 receptors (Bmax, 1.

Time-dependent protective effects of calcium channel blockers on anoxia- and hypoxia-induced proximal tubule injury.

The effects of anoxia or hypoxia on Ca++ uptake and lactic dehydrogenase (LDH) release were examined in freshly isolated rat proximal tubules (rPT). Both Ca++ uptake and LDH release were increased above control after only 10 min of either anoxia or hypoxia in rPT. The increase in Ca++ uptake was through voltage-sensitive, slow Ca++ channels, because pretreatment with chemically dissimilar calcium channel blockers (CCB), either verapamil or flunarizine, prevented the increased Ca++ uptake and reduced the LDH release from the anoxic and hypoxic rPT.

Effect of long-acting calcium entry blocker (anipamil) on blood pressure, renal function and survival of uremic rats.

To assess more completely the long-term effect of a long-acting calcium channel blocker, anipamil was given p.o. to rats with subtotal (five-sixths) nephrectomy.

Progressive renal insufficiency: the role of angiotensin converting enzyme inhibitors.

Experimental animal studies have demonstrated a renal protective effect of ACE inhibition therapy in diabetes mellitus and the remnant kidney model of chronic renal failure. The mechanism of this effect is secondary, at least in part, to the drugs' effects on glomerular hemodynamics. In addition, there is further evidence to suggest that ACE inhibitors may influence other pathogenic mechanisms of progressive renal insufficiency.

Calcium channel blockers: protective effects in ischemic acute renal failure.

Studies in heart, liver, and kidney have provided evidence that calcium is an important factor in cell injury. Calcium channel blockers are used with increasing frequency in ischemic and toxic renal failure. In this review the available data on the effects of calcium channel blockers in animal models of ischemic renal failure are presented and possible mechanisms of protective actions are discussed.

Effect of elevated extracellular glucose concentrations on calcium ion uptake by cultured rat vascular smooth muscle cells.

Blood flow autoregulation is impaired in early diabetes mellitus, predisposing the microvasculature to injury. Blood flow autoregulation is in part a myogenic response that is critically dependent on Ca2+ uptake via voltage-sensitive calcium channels in vascular smooth muscle cells (VSMC). Recent evidence suggests that impairment of blood flow autoregulation in diabetes may be responsive to variations in glycemic control.

Pathogenesis of sodium and water retention in liver disease.

The "Peripheral Arterial Vasodilation" hypothesis most completely explains the clinical spectrum of cirrhosis ranging from compensated to decompensated to the hepatorenal syndrome (Figure 15-1). As the systemic peripheral vasodilation increases, the neurohumoral responses to arterial underfilling are stimulated with resultant renal vasoconstriction, sodium and water retention. Hypoalbuminemia and portal hypertension, as well as local effects of vasodilation at the capillary level, also contribute to ascites formation and peripheral edema.

Human cytomegalovirus productively infects primary differentiated macrophages.

Monocytes are one of the predominant cell types in the peripheral blood that are infected by human cytomegalovirus (HCMV). Although virus can be detected in these cells in vivo, HCMV replication in cultured monocytes has been unsuccessful. In this study, we demonstrate efficient HCMV replication in cultured monocytes.

Reversible renal failure associated with angiotensin-converting enzyme inhibitors in polycystic kidney disease.

The renin-angiotensin-aldosterone system appears to play an important initiating role in the pathogenesis of hypertension in patients with autosomal-dominant polycystic kidney disease (ADPKD). Therefore, angiotensin-converting enzyme (ACE) inhibitors would appear to be appropriate therapy for hypertension in such patients. However, because ADPKD is a bilateral disorder, ACE-inhibitor therapy may worsen renal function, as occurs in patients with bilateral renal artery stenosis.

Unifying hypothesis of sodium and water regulation in health and disease.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients.

Pathogenesis of hypertension in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is a common (approximately 1 in 400 individuals in the United States) inherited disorder, in which hypertension is the most often associated disorder. Although the development of hypertension originates with expansion of renal cysts, it most likely has its pathogenesis in the renal vasculature. Evidence is now accumulating that the renin-angiotensin-aldosterone system is important in the development and maintenance of hypertension in this disorder.

Reduction of remnant nephron hypermetabolism by protein restriction.

To study the metabolic mechanisms involved in the protective effect of dietary protein restriction on the progression of chronic renal failure, experiments were performed in Sprague-Dawley rats subjected to five-sixths nephrectomy and pair-fed on isocaloric low (4%) protein (LP) or high (50%) protein (HP) diets. Protein restriction reduced the severity of uremia, with lower blood urea nitrogen (BUN) concentrations (8.9 +/- 1.

Role of calcium channel blockers in protection against experimental renal injury.

The available evidence indicates that the first generation calcium channel blocker verapamil has a protective effect against both acute and chronic renal failure. At the cell membrane, verapamil helps minimize the effects of excess calcium influx after ischemic injury, evidenced by reduced uptake of 45Ca, thus lessening tubular injury from both calcium-activated phospholipases and mitochondrial calcium overload. In experimental chronic renal failure, the long-term administration of verapamil protects against renal dysfunction and damage, independent of any effect on systemic mean arterial pressure.

Peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy: implications for pathogenesis of preeclampsia-eclampsia.

Primary peripheral arterial vasodilation with relative underfilling of the arterial circulation occurs in early pregnancy and leads to several consequences, including decreased systolic and diastolic blood pressures, enhanced cardiac output secondary to afterload reduction, stimulation of the renin-angiotensin-aldosterone axis, nonosmotic stimulation of thirst and vasopressin release, and renal sodium and water retention with expansion of the extracellular fluid and plasma volume compartments. These are events known to occur in all states of arterial vasodilation. Pregnancy has, however, several unique features.

Immunopathogenesis of HIV encephalitis.

HIV infection leads to severe immunosuppression and in a sub-population of patients, encephalitis. Whether systemic immunosuppression is required for CNS infection is still unclear. However, latent infection of monocytes/macrophages is an important mechanism by which HIV escapes immune surveillance and enters the CNS.

Pathogenesis of HIV encephalitis.

A wide spectrum of infectious agents attack the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients. Human immunodeficiency virus (HIV) itself, infects the CNS of a subgroup of these patients. The mechanism behind why HIV enters the CNS is unclear.

Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention.

In patients with congestive heart failure (CHF), the role of aldosterone in the abnormal sodium (Na+) retention and the determinants of plasma aldosterone (PA) including plasma atrial natriuretic factor (hANF), plasma renin activity (PRA), and plasma potassium (K+) have not been fully elucidated. We therefore studied the effect of the specific aldosterone antagonist, spironolactone, on urinary Na+ and K+ excretion and plasma hormone responses in 6 Na(+)-retaining CHF patients. After withdrawal of diuretics 4 days prior to the study, the CHF patients were placed on a Na+ intake of 100 mmol/day for 9 days.

Mechanisms of rapid desensitization to arginine vasopressin in vascular smooth muscle cells.

This study characterized the rapid desensitization induced by arginine vasopressin (AVP) in vascular smooth muscle cells (VSMC) in culture. The Ca2+ mobilization response and, in some experiments, the intracellular pH changes were used as a probe for the desensitization phenomenon. In VSMC, AVP desensitization was homologous, concentration dependent, and occurred in less than 30 s.

Effects of extra- and intracellular pH on vascular action of arginine vasopressin.

Compared with control studies performed at an extra-cellular pH (pHe) of 7.4, when vascular smooth muscle cells (VSMC) were preincubated in an acid extracellular medium (pHe 7.0) for 60 min the maximal arginine vasopressin (AVP)-induced sustained cellular contraction was reduced, whereas preincubation in an alkaline extracellular medium (pHe 7.

Role of calcium-channel blockers in preventing acute and chronic renal injury.

Calcium-channel blockers (CCBs) have been shown to afford protection against acute (ARF) and chronic renal failure (CRF). The effects of CCBs against acute renal injury occur at both the vascular and tubular epithelial level. At the vascular level, experimental ARF-associated loss of renal autoregulation and hypersensitivity to renal nerve stimulation has been shown to be reversed by CCBs.

The future of calcium channel blocker therapy in diabetes mellitus.

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive.