Inotropic and lusitropic effects of calcitonin gene-related peptide in the heart

Previous studies have demonstrated positive-inotropic effects of calcitonin gene-related peptide (CGRP), but the mechanisms remain unclear. Therefore, two experiments were performed to determine the physiological correlates of the positive-inotropic effects of CGRP. Treatments designed to antagonize the effects of physiologically active CGRP1–37 included posttreatment with CGRP8–37 and pretreatment with LY-294002 (LY, an inhibitor of phosphatidylinositol 3-kinase), 17β-estradiol (E), and progesterone (P) were also used to modulate the effects of CGRP1–37. Experiment 1 was in vitro studies on sarcomeres and cells of isolated adult rat cardiac myocytes. CGRP1–37, alone and in combination with E and P, decreased sarcomere shortening velocities and increased shortening percentages, effects that were antagonized by CGRP8–37, but not by LY. CGRP1–37 increased resting intracellular calcium ion concentrations and Ca2+ influxes, effects that were also antagonized by both CGRP8–37 and LY. Experiment 2 was in vivo studies on left ventricular pressure-volume (PV) loops. CGRP1–37 increased end-systolic pressure, ejection fraction, and velocities of contraction and relaxation while decreasing stroke volume, cardiac output, stroke work, PV area, and compliance. After partial occlusion of the vena cava, CGRP1–37 increased the slope of the end-systolic PV relationship. CGRP8–37 and LY attenuated most of the CGRP-induced changes....
Source: AJP: Heart and Circulatory Physiology - Category: Cardiology Authors: Tags: CARDIOVASCULAR NEUROHORMONAL REGULATION Source Type: research