MECHANISMS OF MYOGENIC ENHANCEMENT BY NOREPINEPHRINE

Mechanisms contributing to the ability of norepinephrine (NE) to enhan ce arteriolar myogenic responsiveness were studied in the rat cremaste r muscle. Anesthetized rats were enclosed in an airtight box that coul d be pressurized to increase intravascular pressure in the cremaster, which was exteriorized into a tissue bath. Vessel diameter, intravascu lar pressure, and red cell velocity were measured in the first-order ( 1A) arteriole during box pressure increases of 10, 20, and 30 mmHg. Co ntrol arterioles [diameter = 113 +/- 3 (SE) mu m] did not exhibit myog enic constriction in response to step increases in intravascular press ure (e.g., +30 mmHg, diameter = 122 +/- 5 mu m), whereas after 25% con striction with NE (diameter = 85 +/- 2 mu m) arterioles exhibited sign ificant myogenic constriction (e.g., +30 mmHg, diameter = 70 +/- 4 mu m) The NE effect on myogenic reactivity was augmented by Ca2+ channel agonists and inhibited by antagonists, suggesting a role for voltage-o perated Ca2+ channels. In contrast to NE, exposure to KCl (30 mM) did not enhance myogenic responsiveness, suggesting that factors in additi on to voltage-operated channels were involved in the NE effect. The pr otein kinase C (PKC) activator indolactam (1 mu M) was found to increa se vascular tone in the 1A arterioles (diameter = 109 +/- 6 to 89 +/- 7 mu m) and to induce significant myogenic responsiveness similar to t hat produced by NE (e.g., +30 mmHg, diameter = 65 +/- 9 mu m). Stauros porine (0.1 mu M) and calphostin C (1 mu M), inhibitors of PKC, signif icantly attenuated the NE-induced myogenic response. Physical factors, e.g., the extent of NE-induced constriction, wall tension, and shear rate could not explain the ability of NE to enhance arteriolar myogeni c responsiveness. The results suggest that both voltage-operated Ca2channels and PKC-mediated events act in adrenergic facilitation of art eriolar myogenic reactivity.