title: Aged spontaneously hypertensive rats exhibit a selective loss of EDHF-mediated relaxation in the renal artery.
abstract: Endothelium-dependent relaxation is frequently attenuated in hypertension. We hypothesized that the contribution of the endothelium-derived hyperpolarizing factor (EDHF) to the acetylcholine (ACh)-induced, endothelium-dependent relaxation is attenuated with aging in the renal artery of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats. ACh-induced, NO-mediated relaxation was identical in young (8-week-old) WKY and SHR, whereas EDHF-mediated relaxations (assessed in the presence of Nomega-nitro-l-arginine and diclofenac) were much more pronounced in SHR than WKY. KCl-induced relaxations were more pronounced in vessels from young WKY rats than from young SHR. The cytochrome P450 inhibitor sulfaphenazole significantly inhibited EDHF-mediated relaxation in vessels from young SHR but not WKY. Vessels from old (22 months) SHR exhibited a slightly reduced NO-mediated relaxation but a complete loss of EDHF-mediated responses. In contrast, aging did not affect EDHF-mediated responses in WKY. Moreover, ACh-induced hyperpolarization and resting membrane potential were decreased in old SHR but not in WKY. KCl-induced relaxation increased with age in WKY, whereas no response to KCl was recorded in arteries from aged SHR. In vessels from old WKY but not old SHR, mRNA expression of the Na-K-ATPase subunit alpha2 was increased by 2-fold compared with young animals. These data indicate that the increase in EDHF responses in renal arteries from aged WKY can be attributed to the release of K+ ions from the endothelium, whereas increased EDHF responses in renal arteries from young SHR can be attributed to a sulfaphenazole-sensitive cytochrome P450-dependent EDHF.
authors.affiliation: Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
authors.forename: Eckhart
authors.initials: E
authors.lastname: Büssemaker
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Popp
authors.forename: Beate
authors.initials: B
authors.lastname: Fisslthaler
authors.forename: Christiana M
authors.initials: CM
authors.lastname: Larson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
authors.forename: Rudi
authors.initials: R
authors.lastname: Busse
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Brandes
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008564:Membrane Potentials; D009924:Organ Culture Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013426:Sulfaphenazole / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D013426:Sulfaphenazole; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine