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Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia
J M Stulak1, A Lerman, J A Caccitolo
1Department of Physiology and Biophysics, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Atherosclerosis
|January 4, 2001
Summary
High cholesterol impairs renal artery function by reducing nitric oxide (NO) availability. This study shows experimental hypercholesterolemia (HC) significantly attenuates renal artery relaxation, highlighting HC as a risk factor for renovascular disease.
Area of Science:
- Cardiovascular Physiology
- Renal Vascular Function
- Metabolic Syndrome
Background:
- Hypercholesterolemia (HC) is known to impair systemic vascular reactivity.
- Endothelial dysfunction, characterized by reduced nitric oxide (NO) activity, is a key feature of HC.
- The impact of HC on renal vascular function remains less understood.
Purpose of the Study:
- To investigate the effects of experimental HC on porcine renal artery function in vitro.
- To determine if HC alters endothelium-dependent relaxation and NO bioavailability in renal arteries.
- To assess the expression of endothelial NO synthase (eNOS) in HC-induced renal arteries.
Main Methods:
- Renal artery segments from pigs fed a HC or normal diet were used for in vitro studies.
- Endothelium-dependent relaxation was assessed using acetylcholine and A23187.
- Nitric oxide synthase inhibition (N(G)-monomethyl-L-arginine) and supplementation (L-arginine) were employed.
- Smooth muscle relaxation and cyclic GMP generation were measured in response to a NO donor (diethylamine).
- Endothelial NO synthase (eNOS) expression was quantified using Western blotting.
Main Results:
- Endothelium-dependent relaxation to acetylcholine was significantly attenuated in HC pigs compared to controls.
- This impaired relaxation was partially restored by L-arginine supplementation.
- Receptor-independent relaxation to A23187 was also blunted in HC renal arteries.
- Smooth muscle relaxation and cyclic GMP generation were enhanced in denuded HC vessels.
- eNOS expression was significantly reduced in renal arteries from HC pigs.
Conclusions:
- Experimental hypercholesterolemia attenuates endothelium-dependent relaxation in porcine renal arteries.
- This dysfunction is likely due to impaired nitric oxide bioavailability and reduced eNOS expression.
- These findings suggest that HC may contribute to the pathogenesis of renal disease and hypertension, reinforcing its role as a risk factor for renovascular disease.