Discrepancy between initial and steady-state resistance vessel responsiveness to short-term nitroglycerin exposure in the hindlimb of conscious dogs.
Since much of the antianginal efficacy of nitroglycerin can be ascribed to its ability to dilate large arteries and venous capacitance vessels at dosages that have little steady-state effect on vascular resistance, we re-examined the reasons for low responsiveness of resistance vessels to nitroglycerin in a peripheral vascular bed in vivo. In chronically instrumented conscious dogs, intra-iliac nitroglycerin (0.15, 0.5, and 1.5 micrograms/kg/min) resulted in substantial dose-dependent initial increases in iliac flow (35% +/- 7%, 60% +/- 11%, and 106% +/- 12%, respectively). However, unlike the responses of iliac large artery diameter, these dilations were not sustained during a 6-min infusion. In contrast, doses of nitroprusside, acetylcholine, and adenosine, which gave initial dilations comparable to nitroglycerin, resulted in considerably greater steady-state responses (p less than 0.001). Nitrate tolerance, autoregulatory escape, reflex vasoconstriction, and the influence of cyclooxygenase products were ruled out as potential explanations of this selective pattern of nitroglycerin response. It is proposed that the rapid attenuation of nitroglycerin-induced dilation in a representative peripheral vascular bed cannot be attributed to currently accepted hypotheses and contributes more to the unique and beneficial spectrum of nitrate vascular action than an a priori lack of sensitivity of resistance vessels.
Stewart
D J
DJ
Department of Medicine, McGill University, Montreal, Canada.
Münzel
T
T
Holtz
J
J
Bassenge
E
E
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001160:Arterioles / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006706:Homeostasis; D007866:Leg / Q000098:blood supply; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D013564:Sympathetic Nervous System / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D005996:Nitroglycerin; D000111:Acetylcysteine