cardiovascular-agents and conivaptan

The role of arginine vasopressin in heart failure and the use of vasopressin receptor antagonists in the treatment of heart failure are reviewed.. Arginine vasopressin (AVP) functions in the regulation of plasma osmolarity and blood pressure. In heart failure, AVP worsens heart failure by causing vasoconstriction of arteries and veins, potentially contributing to remodeling of the left ventricle and causing fluid retention and worsening of hyponatremia. Two V(2)-receptor antagonists, tolvaptan and lixivaptan, and one combined V(1a)- and V(2)-receptor antagonist, conivaptan, have shown promise for use in patients with heart failure. All three agents have been shown to increase free water excretion and increase serum sodium levels while maintaining serum potassium levels. They have not been shown to decrease renal function or the glomerular filtration rate and are well tolerated, with thirst being the major adverse effect during clinical trials. Because of their effects on sodium, vasopressin antagonists need to be carefully monitored to ensure that serum sodium levels do not increase too quickly and put the patient at risk for overcorrection or osmotic demyelination syndrome. In addition, patients need to be monitored for signs of dehydration secondary to increased urine excretion. To date, studies have not consistently shown improvements in patient symptoms or weight reduction. However, early data suggest that at least one agent, tolvaptan, does not alter mortality.. Based on data from available clinical trials, vasopressin antagonists may offer a new treatment option for patients with congestive heart failure. However, these agents do not currently appear to delay the progression of heart failure or decrease mortality.

Topics: Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Azepines; Benzamides; Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure; Humans; Hyponatremia; Pyrroles; Receptors, Vasopressin; Tolvaptan

Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Benzazepines; Cardiovascular Agents; Cell Hypoxia; Cell Survival; Cells, Cultured; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Glucose; Mitochondria; Myocytes, Cardiac; Neurons; Neuroprotective Agents; Rats, Wistar; Receptors, Vasopressin

Topics: Benzazepines; Cardiovascular Agents; Contraindications; Dobutamine; Dopamine; Drug Combinations; Drug Incompatibility; Humans; Infusions, Intravenous; Milrinone; Nitroglycerin

Conivaptan, a dual vasopressin receptor antagonist, is a member of an emerging class of medications for the treatment of euvolemic hyponatremia. These agents induce a free-water diuresis as compared to the natriuretic effect of loop diuretics and make them an intriguing prospect for the treatment of congestive heart failure. Article also includes recent patents on this topic.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiovascular Agents; Diuretics; Heart Failure; Hormone Antagonists; Humans; Patents as Topic; Treatment Outcome; Water-Electrolyte Balance

The systemic hemodynamic and renal responses to conivaptan hydrochloride (YM087; 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine -6-carbonyl)-2-phenylbenzanilide monohydrochloride), a vasopressin V1A and V2 receptor antagonist, were determined in pentobarbital-anesthetized dogs after 2 to 3 weeks of rapid right ventricular pacing. Congestive heart failure, characterized by decreases in first derivative of left ventricular pressure (left ventricular d P/dt(max)) and cardiac output, and increases in left ventricular end-diastolic pressure and total peripheral vascular resistance, was induced by chronic rapid right ventricular pacing at 260-280 beats/min. Intravenous administration of conivaptan (0.1 mg/kg) significantly increased left ventricular dP/dt(max) and cardiac output and significantly decreased left ventricular end-diastolic pressure and total peripheral vascular resistance. Conivaptan also increased urine flow and reduced urine osmolality by markedly increasing free water clearance. These results indicate that conivaptan produced hemodynamic improvement and marked aquaresis in dogs with congestive heart failure. Therefore, conivaptan may find clinical use in treating patients with congestive heart failure.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiac Pacing, Artificial; Cardiovascular Agents; Diuresis; Dogs; Female; Heart Failure; Hemodynamics; Male; Receptors, Vasopressin; Renal Agents