Role ofCGRP in the Regulation of Coronary Blood Flow

In a seminal study concerning the nonadrenergic noncholinergic regulation of basal coronary flow, Yaoita et al. (41) clearly demonstrated that capsaicin-sensitive neuropeptides (primarily CGRP) in the rat's heart provide approx 30% of basal coronary flow modulation. To provide additional evidence that a-CGRP plays a critical role in the

Blood Flow The Heart Steps
Fig. 5. Coronary flow rates are decreased in a-CGRP KO mice. Isolated perfused heart preparations were used to determine coronary flow rates at the indicated perfusion pressures. Data are expressed as the mean ± SEM. *p < 0.05 WT vs KO males and #p < 0.05 for WT vs KO females.

regulation of coronary blood flow, Langendorff-perfused heart preparations were used to compare coronary flow rates between a-CGRP KO and WT control mice under various pressure-loading conditions. Hearts from 33 mice (female, 6 KO and 9 WT; male, 8 KO and 10 WT) were used in this study. Deletion of the a-CGRP gene in both genders resulted in a significant reduction in the coronary flow at all pressures tested (Fig. 5). In addition, coronary flows for both strains of mice were consistently lower in female than in male mice. Therefore, these data suggest that CGRP is responsible for up to 30% of basal coronary blood flow. In addition, based on the histological analysis, there are no obvious structural or pathological alterations in the myocardium or coronary vasculature between the groups. Because blood vessel diameter is directly related to coronary flow, pilot studies were done to determine the range of blood vessel diameters (optical micrometer) in heart sections from the KO and WT mice. No detectable differences were observed between the two strains. Thus, the mechanism of this reduction in coronary flow is likely to decrease coronary vasodilation resulting from an ablation of a-CGRP from perivascular sensory nerve terminals.

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