Lack of Correlation Between Initial Vascular Resistance and Responses to Vasoconstrictor Stimuli in the Perfused Canine Hindpaw 1

Summary

The effect of initial vascular resistance on the vascular responses of the perfused canine hindpaw to nitroglycerin, norepinephrine, tyramine, sympathetic nerve stimulation and angiotensin was evaluated. Initial resistances were altered by (a) vasodilator drugs (nitroglycerin and prostaglandin B₁) and (b) background infusions of norepinephrine and prostaglandin B₂. Over a wide range of initial vascular resistances, the absolute magnitude of dilator responses of the perfused canine hindpaw to nitroglycerin is directly proportional to the level of initial vascular resistance. Over the pressure range of most physiologic and pharmacologic perfusions (80-400 mm Hg; 2.7-18.5 peripheral resistance units), the change in resistance produced by stimulation of the sympathetic nerves and intraarterial norepinephrine, tyramine and angiotensin was independent of the initial vascular resistance and the mode by which these resistances were altered. Although the larger total vascular resistances developed when initial resistances were higher, the magnitude of induced increases in vascular resistance was unchanged. If these results are extrapolated to constant flow perfusion experiments utilizing the canine hindpaw, in which the initial vascular resistance increases as a result of physiologic or pharmacologic interventions, they indicate that changes in response to a given constrictor agonist produced during drug-induced changes in vascular resistance would result from the intrinsic activity of the drug and not secondary to the change in vascular resistance.

The authors gratefully acknowledge the generous gift of prostaglandins from Drs. J. R. Week and J. E. Pike of the Upjohn Co., Kalamazoo, MI. We also express our appreciation to Dr. M. J. Brody for his helpful suggestions and critical appraisal of this manuscript.