Altered responsiveness of diabetic dog renal arteries to acetylcholine and phenylephrine: role of endothelium.
The mechanical responses to acetylcholine (ACh), sodium nitroprusside and phenylephrine (PE) were determined in normal and diabetic dog renal arterial strips with and without endothelium. Experimental diabetes increased the sensitivity, IC50 = (2.9 +/- 0.4) X 10(-8) mol/l in normal and (9.6 +/- 1.5) X 10(-9) mol/l in diabetic (p less than 0.01, n = 6) to ACh of endothelium intact renal arterial strips without influencing the maximum relaxation induced by this agonist. In all intact vessels PE produced contractions of equal magnitude. Removal of the endothelium completely abolished the relaxant ability of ACh, and caused a slight increase in the contractile response of both diabetic and normal strips to PE. The maximum contractile force generated by the denuded diabetic vessels in response to PE was significantly (p less than 0.01) greater than the maximum tension produced by the denuded nondiabetic arteries. The sensitivity of the tissues to PE was, however, not modified by either diabetes or endothelium removal. The direct relaxant sodium nitroprusside elicited a similar degree of relaxation in the two groups of arteries. Cyclooxygenase blockade had no effect on either the relaxation or contractile responses of any of the preparations. These findings suggest that short-term diabetes makes dog renal arteries supersensitive to ACh and hyperreactive to PE.
Gebremedhin
D
D
Semmelweis University of Medicine, Department of Pharmacodynamics, Budapest, Hungary.
Koltai
M Z
MZ
Pogátsa
G
G
Magyar
K
K
Hadházy
P
P
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*
D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine