Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries

Abstract

Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventricular myocytes, may influence coronary vascular tone. We studied the coronary vasodilatory response to BNP under physiological conditions and after preconstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-flow velocity (APV) was measured using intracoronary Doppler, and cross-sectional area (CSA) was measured using intravascular ultrasound. Coronary blood flow (CBF) was calculated. Intracoronary BNP induced dose-dependent increases in CSA, APV, and CBF similar in magnitude to those induced by nitroglycerin (NTG). The magnitude of BNP-induced vasodilation was accentuated after preconstriction with ET-1. Pretreatment with either the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the coronary vasodilator effect of BNP in resistance arteries without influencing epicardial vasodilation. Pretreatment with the ATP-sensitive potassium-channel blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We conclude that BNP exerts coronary vasodilator effects, predominantly in epicardial conductance vessels. An accentuated vasodilatory response to BNP occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary resistance arteries may be partially mediated via nitric oxide and/or prostaglandin release.

Nesiritide, Renal Function, and Associated Outcomes During Hospitalization for Acute Decompensated Heart Failure

“…N esiritide is recombinant B-type natriuretic peptide (BNP) [1][2][3][4] approved for use in patients with acute heart failure, because of its ability to reduce pulmonary-capillary wedge pressure and improve dyspnea. 3,5 Yet after approval, it was suggested that nesiritide might cause renal toxicity and increase mortality.…”

Lack of activation of molecular forms of the BNP system in human grade 1 hypertension and relationship to cardiac hypertrophy

“…natriuretic peptide; brain natriuretic peptide; amino-terminal pro-brain natriuretic peptide; left ventricular hypertrophy BRAIN NATRIURETIC PEPTIDE (BNP) is synthesized in cardiac myocytes as the precursor proBNP, a 108-amino acid peptide (4, 27, 33), and is converted to biologically active peptide BNP32 via a proteolytic cleavage by corin, a type II transmembrane cardiac serine protease (22,38,39). BNP is present in the circulation in two different forms, the biologically active BNP32 that elicits different beneficial cardiorenal and hormonal actions (1,5,8,11,25,26,40) and the amino-terminal portion of BNP (NT-proBNP) that consists of 76 amino acids.In congestive heart failure (CHF) as well as in hypertension (HTN), ventricular cardiomyocytes are progressively recruited to synthesize BNP (24). Whereas initially a successful defensive endocrine response by the heart to preserve cardiorenal homeostasis might occur, a hyporesponsiveness to cardiac peptides, which might contribute in turn to the progression of hypertension, could follow later.…”

“…BNP is present in the circulation in two different forms, the biologically active BNP32 that elicits different beneficial cardiorenal and hormonal actions (1,5,8,11,25,26,40) and the amino-terminal portion of BNP (NT-proBNP) that consists of 76 amino acids.…”

Effects of Intravenous Nesiritide on Human Coronary Vasomotor Regulation and Myocardial Oxygen Uptake

“…BNP has been shown to induce vasodilation in isolated human arterial and venous tissue preparations, 5 in vivo human forearm studies, 6 human pulmonary circulation, 7 and porcine coronary conductance and resistance arteries. 8 Furthermore, human BNP infused into the left main coronary artery or the pulmonary artery has been shown to induce epicardial artery vasodilation. 9 The effects of intravenous nesiritide on the coronary circulation in humans have not been evaluated.…”