title: Effect of endogenous natriuretic peptide system on ventricular and coronary function in failing heart.
abstract: Ventricular concentrations of atrial, brain (BNP) and C-type natriuretic peptide are enhanced in congestive heart failure (CHF). Natriuretic peptide receptors are present on ventricular myocytes and stimulate guanosine 3',5'-cyclic monophosphate (cGMP) production. cGMP has been demonstrated to affect myocyte function in vitro. Thus we hypothesized that the intracardiac natriuretic peptide system may modulate myocardial and coronary function in CHF. To test this hypothesis, the effects of an intracoronary infusion of the natriuretic peptide receptor antagonist HS-142-1 on ventricular and coronary function were examined in anesthetized dogs with chronic CHF. To determine whether receptor stimulation had contrasting effects to those of receptor blockade, intracoronary BNP was infused in anesthetized normal and CHF dogs. Low-dose HS-142-1 delayed and slowed left ventricular (LV) relaxation and decreased coronary blood flow without changes in LV pressures. Higher doses further impaired LV relaxation without further decreases in coronary blood flow. In normal and CHF dogs, exogenous BNP produced the opposite effect with a quicker onset and faster rate of LV relaxation without effects on LV pressures or coronary blood flow. The endogenous natriuretic peptide system has an autocrine-paracrine role to modulate LV and coronary vascular function in CHF.
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
authors.forename: M M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D009202:Cardiomyopathies / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D013610:Tachycardia; D014655:Vascular Resistance; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; C072551:HS 142-1; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011412:Propanolamines; D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; C036604:esmolol