Enhanced acetylcholine-induced dilation in afferent arterioles in simvastatin-fed rats.
OBJECTIVE
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to increase renal blood flow and glomerular filtration rate independent of their lipid lowering effects. The purpose of this study was to determine the effect of simvastatin on acetylcholine-induced vasodilation in the renal microcirculation. The hypothesis of the study was that simvastatin would increase acetylcholine-induced vasodilation in the renal microcirculation.


METHODS
The hydronephrotic kidney preparation was used. On the day of the experiment the kidney was prepared for videomicroscopy and dose-response curves were done with acetylcholine and sodium nitroprusside (10(-10) M to 10(-5) M) in simvastatin-fed rats ??(n=8) and control rats (n=13). The vasodilator responses of afferent and efferent arterioles were directly quantitated using videomicroscopy. L-NAME; (N(omega)-nitro-L-arginine methyl ester) was also given in a group of simvastatin-fed rats (10(-5) M) to determine if it would block the acetylcholine (Ach)-induced vasodilation.


RESULTS
Simvastatin enhanced Ach-induced vasodilation in the afferent arteriole compared to control rat responses to Ach. At 10(-7) M, ACH caused a 31.6+/-7.2% increase from baseline diameter in the afferent arteriole in the simvastatin-fed rats compared to a 23+/-8.1% vasodilation in the control rats (p<0.05). There were no differences in the response to ACH in the efferent arteriole between the two groups. L-NAME completely abolished the ACH response in the simvastatin-fed rats.


CONCLUSIONS
The increase in renal blood flow and glomerular filtration rate observed with simvastatin may be due to its preglomerular vasodilator effects. This may be due to an increase in nitric oxide production.
Inman
Sharon R
SR
Department of Biomedical Sciences, Ohio University College of Osteopathic Medicine, 338 Irvine Hall, Athens, OH 45701, United States. inmans@ohio.edu
Caprio
Timothy W
TW
Drummond
Emily
E
Mueller
M
M
Entenman
Kyle
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D004032:Diet; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006869:Hydronephrosis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D018715:Microscopy, Video; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester