Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principal goals of treatment of the patient in heart failure are the relief of their symptoms and improvement in their prognosis. Of all antiheart failure drugs currently available, the diuretics are therapeutically superior in their efficacy in relieving clinical symptoms and signs. Whether administered intravenously or orally, all diuretics result in a substantial reduction in the raised pulmonary vascular pressures in combination with a small reduction in cardiac output. Diuretics stimulate release of renin with subsequent activation of the renin-angiotensin-aldosterone system, particularly if used in large doses, although their quantitative impact on the neuroendocrine profile at different stages of heart failure remains to be defined. In patients with mild heart failure, diuretics reduce plasma catecholamine concentrations, but their sympatholytic effects in more severe cases are unknown, as are their effects on the metabolically active tissues in these patients. Diuretic resistance can be circumvented by segmental nephron blockade with a combination of low-dose diuretics that simultaneously block sodium reabsorption in the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Diuretics improve symptoms of breathlessness and signs of peripheral edema in patients with congestive heart failure in direct relationship to the induced diuresis. These benefits are frequently associated with a substantial improvement in patients' appreciation of quality of life and economic capacity. There are few adverse reactions to chronic diuretic therapy, but the serum electrolytes should be monitored for hypokalemia and hypomagnesemia. The impact of diuretics on prognosis of patients with congestive heart failure is unknown; however, diuretics have been a major ingredient of the therapies used in all the survival trials with vasodilators, angiotensin-converting enzyme inhibitors, and beta-blocking drugs. In addition to their clinical benefits, diuretics are the most cost-effective treatment of any single drug group currently available for the treatment of patients with congestive heart failure.
Cardiol Rev
PMID:Diuretic therapy in congestive heart failure. 1117 82

Low-renin hypertension is common and usually implies increased retention of sodium (Na(+)). In every case of known etiology, there is a mineralocorticoid-induced increase in number of epithelial Na(+) channels (ENaCs) in the collecting duct of the kidney, leading to a state of "hyperENaCactivity." In primary aldosteronism, a result of either an adrenal adenoma or bilateral adrenal hyperplasia, aldosterone itself mediates the increase in ENaC function. A severe form of low-renin hypertension in which a molecular mutation in ENaC prevents removal of the channel from the cell surface, known as Liddle's syndrome, results in increased net ENaC activity but, in this case, independently of an increase in aldosterone. Glucocorticoid remedial aldosteronism, an autosomal dominant form of primary aldosteronism, results from a "new" or chimeric gene for aldosterone synthase. Adrenocorticotropic hormone stimulates its expression as well as secretion of aldosterone. Apparent mineralocorticoid excess results from a molecular mutation that allows cortisol to bind to the mineralocorticoid receptor. Both glucocorticoid remedial aldosteronism and apparent mineralocorticoid excess result in an increase in the number of ENaCs. The question remains whether low-renin essential hypertension is related to an increase in ENaC activity. Low-renin hypertension is most common in black patients, who tend to have lower levels of aldosterone as well as renin, which are features that resemble those found in Liddle's syndrome. Preliminary findings suggest that black patients with low-renin hypertension who are resistant to standard antihypertensive therapy respond favorably to the addition of spironolactone, a mineralocorticoid receptor antagonist that reduces ENaC activity.
Cardiol Rev
PMID:Low-renin hypertension: more common than we think? 1117 96

Hyponatremia is common and associated with adverse outcomes in patients with congestive heart failure (CHF). In many patients who have CHF with hyponatremia, plasma arginine vasopressin (AVP) is elevated inappropriately. AVP causes water retention by interacting with V2 receptors in the renal collecting duct, leading to dilutional hyponatremia and increased ventricular preload. AVP also may contribute to pathophysiologic process in CHF by interacting with V(IA) receptors on vascular smooth muscle cells and myocytes. The potential utility of AVP antagonists--V2 antagonists and dual V(IA)/V2 antagonists--in correcting hyponatremia and relieving the congestion and edema associated with CHF is being actively explored. Combined antagonists may offer additional benefit by interfering with excessive V(IA) signaling. Unlike diuretics, which increase urine volume and electrolyte excretion, AVP antagonists of these types produce an aquaresis characterized by an increase in free water clearance concomitant with sparing of electrolytes. Studies in experimental CHF as well as preliminary clinical trials with selective and nonselective V2 antagonists have been encouraging, suggesting that these agents may hold promise for treatment of hyponatremia in CHF.
Curr Cardiol Rep 2006 May
PMID:Treating hyponatremia in heart failure. 1755 85

Patients with heart failure often show increased arginine vasopressin secretion and enhanced sympathetic and renin-angiotensin-aldosterone activation, which accelerate renal water reabsorption, causing water retention and volume overload. Tolvaptan is an orally active antagonist of arginine vasopressin type 2 receptors in the collecting duct of the kidney that inhibits water reabsorption without substantially affecting the electrolyte balance. Tolvaptan in combination with conventional diuretics improves fluid retention and congestive symptoms in patients with heart failure and volume overload, with minimal effects on hemodynamics and serum potassium. Tolvaptan slightly increases serum sodium concentrations, generally within the normal range. Although it does not seem to affect long-term mortality, tolvaptan does improve short-term water retention and congestive symptoms in heart failure patients with volume overload despite the use of conventional diuretics, and is approved for this indication in Japan.
Future Cardiol 2013 Mar
PMID:Tolvaptan for the treatment of hyponatremia and hypervolemia in patients with congestive heart failure. 2346 68