Abstract
We investigated whether renovascular hypertension alters vasodilatation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing
factor (EDHF) and the influence of the superoxide dismutase mimetic tempol on vasodilatation. One-kidney one-clip hypertensive
Sprague–Dawley rats, treated with either vehicle or tempol (from weeks 5 to 10 after placement of the clip), and uninephrectomized control rats
were investigated. In renal hypertensive rats systolic blood pressure increased to 171±6 mmHg (n=10), while in tempol-treated rats systolic blood
pressure remained normal (139±7 mmHg, n=5). In isolated pressurized mesenteric small arteries NO-mediated dilatation was obtained by
increasing flow rate and EDHF-mediated dilatation by acetylcholine. In arteries from hypertensive rats, flow-induced dilatation was blunted, as
compared to normotensive and tempol-treated rats, while acetylcholine-induced dilatation remained normal. Measured by dihydroethidium
staining there was an increased amount of superoxide in arteries from vehicle-treated rats, but not from tempol-treated rats. Expression by
immunoblotting of endothelial NO synthase and the NAD(P)H oxidase subunit p47phox remained unaffected by high blood pressure and tempol
treatment. Simultaneous measurements of NO-concentration and relaxation were performed in isolated coronary arteries from the same animals.
As compared to vehicle-treated rats, both acetylcholine-induced relaxation and NO-concentration increased in arteries from tempol-treated
animals, while only the relaxation was improved by the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In conclusion renovascular
hypertension selectively inhibits flow-induced NO-mediated vasodilatation, while EDHF-type vasodilatation remains unaffected, suggesting that
high blood pressure leads to increased generation of superoxide contributing to decreased NO bioavailability. Furthermore, the abnormal
endothelium function can be corrected by tempol treatment, but this seems to involve mechanisms partly independent of NO.
factor (EDHF) and the influence of the superoxide dismutase mimetic tempol on vasodilatation. One-kidney one-clip hypertensive
Sprague–Dawley rats, treated with either vehicle or tempol (from weeks 5 to 10 after placement of the clip), and uninephrectomized control rats
were investigated. In renal hypertensive rats systolic blood pressure increased to 171±6 mmHg (n=10), while in tempol-treated rats systolic blood
pressure remained normal (139±7 mmHg, n=5). In isolated pressurized mesenteric small arteries NO-mediated dilatation was obtained by
increasing flow rate and EDHF-mediated dilatation by acetylcholine. In arteries from hypertensive rats, flow-induced dilatation was blunted, as
compared to normotensive and tempol-treated rats, while acetylcholine-induced dilatation remained normal. Measured by dihydroethidium
staining there was an increased amount of superoxide in arteries from vehicle-treated rats, but not from tempol-treated rats. Expression by
immunoblotting of endothelial NO synthase and the NAD(P)H oxidase subunit p47phox remained unaffected by high blood pressure and tempol
treatment. Simultaneous measurements of NO-concentration and relaxation were performed in isolated coronary arteries from the same animals.
As compared to vehicle-treated rats, both acetylcholine-induced relaxation and NO-concentration increased in arteries from tempol-treated
animals, while only the relaxation was improved by the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In conclusion renovascular
hypertension selectively inhibits flow-induced NO-mediated vasodilatation, while EDHF-type vasodilatation remains unaffected, suggesting that
high blood pressure leads to increased generation of superoxide contributing to decreased NO bioavailability. Furthermore, the abnormal
endothelium function can be corrected by tempol treatment, but this seems to involve mechanisms partly independent of NO.
| Originalsprog | Dansk |
|---|---|
| Tidsskrift | European Journal of Pharmacology |
| Vol/bind | 566 |
| Udgave nummer | (1-3) |
| Sider (fra-til) | 160-166 |
| Antal sider | 7 |
| ISSN | 0014-2999 |
| Status | Udgivet - 2007 |