Differentiated effects of vasodilators on myogenic reactivity during partial inhibition of myogenic tone in pressurized skeletal muscle small arteries of the rat

Abstract

Myogenic tone and reactivity were studied in isolated, cannulated and pressurized small branches of the femoral artery of the rat. Myogenic tone developed spontaneously under control conditions (1.5 mM Ca2+), reducing the diameter at 80 mmHg to 64 +/- 6% of the 'max 80', i.e. the diameter in Ca2+ free solution, which was 221 +/- 23 microns (mean +/- SD, n = 18). The calcium channel blockers verapamil and diltiazem, dose-dependently, decreased this myogenic tone with pIC50 values of 6.9 +/- 0.2 (n = 7) and 6.6 +/- 0.1 (n = 6), respectively. Myogenic reactivity was demonstrated under control conditions as a sustained decrease in diameter, by 5 +/- 3% of max 80 (after an initial, transient distension), in response to a step increase in transmural pressure from 80 to 140 mmHg. This response to the pressure increase was markedly inhibited when myogenic tone had been reduced by 50% with verapamil or diltiazem resulting, in fact, in an increased steady state diameter by 2 +/- 1 and 1 +/- 1% at 140 compared with 80 mmHg. However, if myogenic tone was reduced to the same extent by low extracellular Ca2+ (approximately 0.3 mM) the vessels constricted by 6 +/- 1% in response to the pressure increase, an effect comparable to that in control Ca2+. Moreover, 50% reductions in myogenic tone by ACh (approximately 0.1 microM) or pinacidil (approximately 0.3 microM) were associated with significantly enhanced reactivity; steady state diameter decreased by as much as 11 +/- 4 and 15 +/- 5% of max 80. These results suggest that voltage dependent L-type Ca2+ channels are involved both in myogenic tone and in the myogenic response to a rise in vascular transmural pressure in skeletal muscle arteries. Partial inhibition of myogenic tone by other pharmacological routes do not necessarily interfere with myogenic reactivity since the response was, in fact, enhanced in the presence of ACh or pinacidil.