Increased vasodilator response to acetylcholine of renal blood vessels from diabetic rats.
The vasodilator effect of acetylcholine (ACh) and nitroprusside and the vasoconstrictor effect of noradrenaline was assessed in the perfused kidney of streptozocin diabetic rats. Compared with control animals injected with acidified saline, the renal vasoconstrictor effect of noradrenaline was increased in diabetic rats both in terms of the dose required to produce 50% of the maximal effect (EC50) and in the maximal response achieved. The renal vasodilator effect of ACh (but not nitroprusside) was similarly enhanced in diabetic animals. The effect of ACh (but not nitroprusside) in the perfused kidney of both control and diabetic rats was reduced or abolished by mepacrine (10 microM), metyrapone (10 microM) or methylene blue (100 microM) suggesting that ACh exhibits vasodilator activity in the rat kidney by virtue of releasing endothelium derived relaxing factor (EDRF). These results are in contrast to previous published reports demonstrating reduced biosynthesis of EDRF in the aorta of diabetic rats. The mechanism which underlies the increased renal vascular response to ACh is not known. However, increased endothelial cell turnover or cholinoceptor number, elevated activity of enzyme(s) which synthesis EDRF or hyperresponsiveness of vascular smooth muscle to released EDRF should all be considered.
Bhardwaj
R
R
Department of Pharmacology, King's College, University of London, UK.
Moore
P K
PK
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000523:psychology; D004327:Drinking Behavior / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014554:Urination / Q000187:drug effects; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine