Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit.
In atherosclerotic rabbits (SCLER), decreases in vascular resistance in response to acetylcholine (ACH), an endothelium-dependent agent, are suppressed, whereas those to nitroprusside (NP), an endothelium-independent vasodilator, are preserved. To determine whether defective vasodilation in SCLER is related to altered reactivity of resistance vessels, we visualized arterioles of rabbit cremaster muscle by videomicroscopy. Arteriolar diameter was monitored during topical (superfusional) delivery of ACh and NO, interventions that did not affect systemic hemodynamics. Diameter changes in response to NP (0.01-100.0 microM) did not differ between SCLER and controls; maximal dilations amounted to 110 +/- 10% (mean +/- SE). In contrast, responses to ACH (0.001-100 microM) differed; maximal dilations averaged 54 +/- 4% in SCLER and 124 +/- 9% in controls (P less than 0.001). These differences persisted after blockade with phentolamine, propranolol, and indomethacin. Phenidone and hydroquinone blockers of endothelium-dependent vasodilation, inhibited arteriolar dilation to ACH without affecting that to NP. Microvascular responses to intra-arterial drug were similar to those elicited by topical drug. Thus, hypercholesterolemia and atherosclerosis in the rabbit appear to produce a microvascular defect characterized by an impaired endothelium-dependent dilation and a preserved endothelium-independent dilation. This defect could play a role in limiting vasodilator reserve in atherosclerosis.
Yamamoto
H
H
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Bossaller
C
C
Cartwright
J
J
Henry
P D
PD
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001161:Arteriosclerosis / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D006873:Hydroquinones / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008853:Microscopy / Q000379:methods; D009132:Muscles / Q000098:blood supply*; D009599:Nitroprusside / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D013690:Television; D014664:Vasodilation / Q000187:drug effects*
D006873:Hydroquinones; D011720:Pyrazoles; D009599:Nitroprusside; D001285:Atropine; D011433:Propranolol; C015429:phenidone; D000109:Acetylcholine; C031927:hydroquinone; D007213:Indomethacin; D010646:Phentolamine