Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit

• Published in: The Journal of clinical investigation Vol. 81; no. 6; pp. 1752 - 1758
• Main Authors: YAMAMOTO, H, BOSSALLER, C, CARTWRIGHT, J. JR, HENRY, P. D
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.06.1988
• Subjects: Acetylcholine - pharmacology; Animals; Arterioles - physiopathology; Arteriosclerosis - physiopathology; Atherosclerosis (general aspects, experimental research); Atropine - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Cardiology. Vascular system; Dose-Response Relationship, Drug; Heart Rate; Hydroquinones - pharmacology; Indomethacin - pharmacology; Male; Medical sciences; Microscopy - methods; Muscles - blood supply; Nitroprusside - pharmacology; Phentolamine - pharmacology; Propranolol - pharmacology; Pyrazoles - pharmacology; Rabbits; Television; Vasodilation - drug effects; Vertebrata; Experimental disease; Mammalia; Microscopy; Arteriole; Atherosclerosis; Rabbit; Cardiovascular disease; Lagomorpha; Video recording; Vasodilation; Cholinergic transmission
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci113516

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.