© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Vasodilator dysfunction in aged spontaneously hypertensive rats: changes in NO synthase III and soluble guanylyl cyclase expression, and in superoxide anion production
aInstitut für Kardiovaskuläre Physiologie, Zentrum der Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
bPGU Cardiovascular agents, Hoechst Marion Roussel, Frankfurt/Main, Germany
* Corresponding author. Tel. (+49-69) 6301 6052; Fax (+49-69) 6301 7668; E-mail: r.busse@em.uni-frankfurt.de
Objective/Methods: Genetic hypertension is associated with an apparent endothelial dysfunction and impaired endothelium-dependent vasodilatation in response to increased flow and receptor-dependent agonists. However, the link between impaired vasodilatation and nitric oxide (NO) synthase expression is still unclear. In the present study, dilator responses were determined in the aorta and coronary circulation of 16 month old spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY). Changes in vascular reactivity were compared with alterations in superoxide anion production as well as endothelial NO synthase (NOS III) and soluble guanylyl cyclase expression. Results: In the isolated perfused heart both the bradykinin- and sodium nitroprusside-induced vasodilator responses were attenuated in SHR compared to WKY. Western blot analysis revealed a parallel reduction in NOS III expression in coronary microvascular endothelial cells from SHR. Superoxide anion production in aortae from SHR was markedly elevated over that of aortae from WKY, and was almost completely abolished by pretreatment with superoxide dismutase. Superoxide dismutase induced similar relaxations in phenylephrine-preconstricted aortic rings from both SHR and WKY, but failed to restore the attenuated acetylcholine- and sodium nitroprusside-induced relaxations in SHR. No difference in NOS III expression was detected in the aortae from either strain whereas soluble guanylyl cyclase expression was markedly decreased in SHR. Conclusions: These results demonstrate that NOS III expression in different tissues is differentially affected by hypertension. Moreover, althoug an elevated superoxide anion production is apparent in the aorta, a reduced soluble guanylyl cyclase expression appears to account for the observed vasodilator dysfunction in SHR.
KEYWORDS Hypertension; Endothelium; Smooth muscle; NO synthase; Superoxide anion; Soluble guanylyl cyclase; Spontaneously hypertensive rats
1 Present address: Klinikum Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany.
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