Abstract

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), a-CGRP gene knockout (KO) and NK1-KO 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 a-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 a-CGRP-KO mice was consistently lower in female than in male mice, but not for NK1-KO mice. Coronary flow rate ina-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 a-CGRP-KO mice, but not in NK1-KO mice.

Key words: Calcitonin gene-related peptide, flow rate, gene knockout, heart, mouse, neurokinin 1, substance P.

Abbreviation