Maintenance of normal agonist-induced endothelium-dependent relaxation in uraemic and hypertensive resistance vessels.
BACKGROUND
The nitric oxide system has been implicated in several diseases with vascular complications including diabetes mellitus and hypertension. Despite the high prevalence of hypertension and cardiovascular complications in renal failure few studies have examined vascular and endothelial function in uraemia. We therefore chose to study possible abnormalities of the nitric oxide vasodilator system in an animal model of chronic renal failure.


METHODS
Adult spontaneous hypertensive rats and Wistar Kyoto rats were subjected to a 5/6 nephrectomy with control animals having sham operations. After 4 weeks blood pressure was recorded and the animals were sacrificed. Branches of the mesenteric arteries were isolated and mounted on a Mulvany myograph. All experiments were performed in the presence of indomethacin (10(-5) M). The vessels were first preconstricted with noradrenaline, exposed to increasing concentrations of acetylcholine (10(-8) to 10(-4) M) and subsequently to sodium nitroprusside (10(-5) M).


RESULTS
There was no difference in the relaxation of the four groups of vessels to any of the concentrations of acetylcholine used nor was there any significant difference in the EC50s (control Wistar Kyoto 6.1+/-1.4 x 10(-8) M; uraemic Wistar Kyoto 5.4+/-0.8 x 10(-8) M; control spontaneous hypertensive rats 4.5+/-0.6 x 10(-8) M; uraemic spontaneous hypertensive rats 6+/-0.7 x 10(-8) M). Vasodilatation in response to sodium nitroprusside was unchanged in uraemic vessels. In addition the vascular responses to both acetylcholine and sodium nitroprusside were unaltered in spontaneous hypertensive rats.


CONCLUSIONS
We conclude that normal agonist-induced endothelium-dependent relaxation is maintained in experimental uraemia and hypertension.
Thuraisingham
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RC
Anthony Raine Research Laboratory, St Bartholomew's Hospital, London, UK.
Raine
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AE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006400:Hematocrit; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009213:Myography; D009392:Nephrectomy; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014511:Uremia / Q000150:complications / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009599:Nitroprusside; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin