Effects of nifedipine on vascular waterfall and arterial resistance in canine hindlimb

Abstract

Pressure-flow relations in the canine hindlimb can be well explained by a vascular waterfall at the arteriolar level. Under these conditions, P(art) = Pcrit + Q.Rart, where P(art) is the arterial pressure, Pcrit is the waterfall pressure, Q is regional flow, and Rart is the arterial resistance of the vessels upstream from the waterfall. To determine whether calcium channels in vascular smooth muscle affect Pcrit in addition to Rart, we pump perfused canine hindlimbs and measured both variables over a range of perfusion pressures (Pper) before and during the infusion of the calcium channel blocker nifedipine. Nifedipine significantly decreased Pcrit and Rart at each Pper. Increasing Pper under control conditions from 50 to 150 mmHg significantly increased Pcrit from 24.2 +/- 1.5 to 42.5 +/- 2.2 mmHg. During nifedipine infusion, increasing Pper from 25 to 100 mmHg also increased Pcrit from 14.5 +/- 1.5 to 20.2 +/- 1.9 mmHg, but the rate of increase was less. In contrast to the rise in Pcrit with increasing Pper, Rart significantly decreased from 10.7 +/- 1.1 to 8.1 +/- 1.2 mmHg.min.100 g.ml-1 before nifedipine infusion, and from 5.7 +/- 0.4 to 2.2 +/- 0.1 mmHg.min.100 g.ml-1 during nifedipine infusion. Venous resistance (Rven) significantly decreased with increases in Pper and during nifedipine infusion. The regional elastic recoil pressure (Pel, a measure of small venular pressure) increased with both an increase in Pper and nifedipine. These results suggest that nifedipine decreases Pcrit, Rart, and Rven and that at constant Pper nifedipine increases Pel.

Ocular pulse amplitude is reduced in patients with advanced retinitis pigmentosa

“…Nitrates act via pronounced vasodilatation of venous capacity vessels by liberating nitric oxide, which is also an endogenous vasodilator from the vascular endothelium,32 39 whereas calcium channel blockers primarily reduce arterial resistance by blocking calcium influx into the vascular smooth muscle cell40 and by inhibiting the endothelial vasoconstrictor, endothelin-1 41…”

Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma

“…This effect is probably due to the calcium channel blocker’s pharmacological mode of action. Calcium channel blockers primarily reduce arterial resistance by blocking calcium influx into the vascular smooth muscle cell42 and by inhibition of the endothelial vasoconstrictor endothelin-143 44 elevated in peripheral blood samples of NTP patients 45. Up to now calcium channel blockers were the only drugs known to increase OPA in a subgroup of glaucoma patients 3…”

Critical Closing Pressure as the Arterial Downstream Pressure with the Heart Beating and during Circulatory Arrest

“…However, the arterial system as a whole, as well as regional arterial circulations, [2][3][4] behave like a Starling resistor in several settings, since blood flow ceases at positive arterial pressures well above venous pressure. [2][3][4][5][6][7][8] Such an arterial pressure has been designated critical closing pressure (P crit ). 2,9 Since P crit is altered by vasoactive drugs 6,10 -12 and tissue warming, 13,14 this behavior is thought to be caused by arteriolar tone 9,10,15 and/or tissue pressure surrounding the vasculature.…”