vasoactive-intestinal-peptide and Cardiac-Output--Low

Vasoactive intestinal peptide (VIP) is a peptidergic neurotransmitter and a vasodilator with positive inotropic and chronotropic properties. Whether and how VIP contributes to the neuroendocrine response in heart failure (HF) is disputed, and there are no data on VIP in pressure overload-induced HF.. We studied 129 adults with isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 48 patients, also from the coronary sinus for determination of VIP by radioimmunoassay. HF was diagnosed according to the European Society of Cardiology criteria.. Plasma VIP (mean+/-S.E.M.) was slightly higher in patients with HF (22.6+/-0.9 pmol/l, n=41) than in patients free of HF (21.1+/-0.5 pmol/l, n=88) or in 11 control patients without structural heart disease (20.0+/-1.3 pmol/l, n=11) (p=0.030 across the groups). VIP did not correlate with any measurement of cardiac structure or function in AS. The change in plasma VIP from aortic root to coronary sinus averaged +1.2+/-0.4 pmol/l in the 11 control patients (p=0.021), +1.2+/-0.2 pmol/l in 33 AS patients free of HF (p<0.001) and +0.8+/-0.3 pmol/l in 15 AS patients with HF (p=0.037).. Both structurally normal and diseased hearts release VIP into the coronary sinus. Although marginally elevated in the systemic circulation, VIP is unlikely to contribute significantly to the neuroendocrine activation in HF due to pressure overload.

Topics: Adult; Cardiac Output, Low; Heart Ventricles; Humans; Myocardium; Radioimmunoassay; Vasoactive Intestinal Peptide

We investigated vasoactive intestinal peptide (VIP)-receptor pharmacology in failing and nonfailing human ventricular myocardium by examining [125I]VIP binding in membrane fractions of left ventricle and inotropic effects of VIP in isolated right ventricular trabeculae mounted in tissue baths. [125I]VIP binding demonstrated upwardly concave, curvilinear Scatchard plots consistent with two classes of binding sites. Only the high-affinity (dissociation constant [Kd] 400-800 pM) site could be regulated by guanine nucleotides. Compared with nonfailing heart, membranes derived from failing heart exhibited a twofold reduction in the Kd of the high-affinity VIP binding site, whereas the receptor density (Bmax) was decreased by 62%. In concordance with this decreased receptor density and increased affinity, the maximal contractile response of right ventricular trabeculae from failing right ventricles was decreased by 61%, and the dose-response curve to VIP was left-shifted approximately threefold. We conclude that the VIP receptor in failing human ventricular myocardium exhibits novel regulatory behavior consisting of increased receptor affinity and decreased receptor density.

Topics: Binding Sites; Cardiac Output, Low; Dose-Response Relationship, Drug; Heart Ventricles; Humans; In Vitro Techniques; Isoproterenol; Myocardial Contraction; Myocardium; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; Reference Values; Vasoactive Intestinal Peptide