Abstract

Hongbao Ma*, Jenny Young and Shen Cherng

Calcitonin gene-related peptide (CGRP) and substance P (SP) which is potent vasodilator neuropeptides play a counter-regulatory role in several models of experimental hypertension. Langendorff-perfused mouse hearts (n = 328) were used to compare coronary flow rates among wild type (WT), -CGRP gene knockout (KO) and NK1KO mice under various pressure loading conditions (20, 30, 40 and 50 mmHg). The aorta of each heart was cannulated and all hearts were perfused with PBS at 37°C. Coronary flow rate was measured by pressure difference of both sides of a capillary. Perfusion was stopped 15 min for ischemia. Deletion of -CGRP gene resulted in a significant reduction in coronary flow rate for both genders at all pressures. Deletion of NK1 gene resulted in a significant reduction in coronary flow rate for male mice at all pressures, but not for female mice. Coronary flow rate for both WT and -CGRP-KO mice was consistently lower in female than in male mice, but not for NK1- KO mice. Coronary flow rate in -CGRP mice was 19.2 and 15.4% lower than that of female and male WT mice, respectively. This effect seems to be gender related with less coronary flow noted in female WT and -CGRP-KO mice, but not in NK1-KO mice.