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Increased spontaneous tone in renal arteries of spontaneously hypertensive rats

Department of Pharmacology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong

Submitted 8 March 2007 ; accepted in final form 1 June 2007

The spontaneous tone of vascular smooth muscle is augmented in hypertension. The present study examined the role of nitric oxide (NO), cyclooxygenase (COX), thromboxane A₂/prostanoid (TP) and PGE₂/prostanoid (EP-1) receptors, reactive oxygen species, and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels in the regulation of spontaneous tone in renal arteries of young and mature Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of arteries, with and without endothelium, were suspended in a myograph for isometric force recording. Spontaneous tone (increase above initial tension) was observed only in arteries of mature SHR and was greater in arteries without endothelium. N-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthases) induced larger contractions in arteries of SHR than WKY. Indomethacin (a COX inhibitor), SC-19220 (an EP-1 receptor antagonist), and terutroban (a TP receptor antagonist) reduced the L-NAME-evoked contractions. Tiron (a superoxide anion scavenger), catalase (an enzyme that degrades H₂O₂), and deferoxamine (a hydroxyl radical scavenger) augmented the L-NAME-induced contractions in arteries of mature SHR. Charybdotoxin (a BK_Ca channel blocker) caused contractions in arteries of mature SHR without endothelium and in arteries with endothelium incubated with L-NAME. A decreased protein level of endothelial NO synthase, an increased release of prostacyclin, and an increased expression of EP-1 receptors were observed in arteries of mature SHR. The present study suggests that spontaneous tone is precipitated by age and hypertension. The reduced production of NO, leading to decreased activation of BK_Ca channels, may leave the actions of endogenous vasoconstrictors unopposed. COX products that activate EP-1 and TP receptors are involved in the development of spontaneous tone.

nitric oxide; cyclooxygenase; large-conductance calcium-activated potassium channels

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