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KMID : 0358619940280020181
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Korean Journal of Physiology
1994 Volume.28 No. 2 p.181 ~ p.190
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Effects of cGMP on the Contractility and Ca Movement in the Aorta of Normotensive Wistar-Kyoto Rats and Spontaneously Hypertensive Rats
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Park Hae-Kun
Jeon Byeong-Hwa
Kim Se-Hoon
Kim Hoe-Suk
Chang Seok-Jong
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Abstract
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Endothelium-derived relaxing factor (EDRF) activates guanylate cyclase which mediates the formation of cGMP from GTP in vascular smooth muscle. It is well known that endothelium-dependent relaxation is impaired in spontaneously hypertensive rats (SHR). However, it is still unknown whether the impaired endothelium-dependent relaxation in SHR results from the reduced release of EDRF or from the decrease of vascular response to EDRF. We investigated the effects of cGMP on the contractility and Ca movement in the aorta of SHR and Wistar-Kyoto rats (WKY). The amplitude of the endothelium-dependent relaxation to actylcholine (ACh) was significantly less in SHR than in WKY. L-arginine did not increase endothelium-dependent relaxation in both strains. Sodium nitroprusside (SNP), an activator of guanylate cyclase, relaxed the 40 mM contraction in a dose-dependent manner in the endothelium-rubbed aortic strips of both strains. However, there was no significant difference in these relaxations between WKY and SHR. 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP), a cell membrane-permeable derivative of cGMP relaxed the 40 mM contraction in a dose-dependent manner in the endothelium-rubbed aortic strips of both strains. Also norepinephrine contractions in normal and Ca-free Tyrode’s solution were suppressed by the pretreatment with 8-Br-cGMP in either strain. However, the amplitudes of suppression induced by 8-Br-cGMP were greater in SHR than that in WKY. Basal uptake and 40mM uptake were not suppressed by pretreatment with 8-Br-cGMP in single aortic smooth muscle cells of both SHR and WKY. From the above results, it is suggested that cGMP decreases Ca sensitivity in vascular smooth muscle cells and that the impaired endothelium-dependent relaxation in the aortic strips of SHR is not the result of a reduced vascular response to EDRF.
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KEYWORD
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Cyclic GMP, Sodium nitroprusside, Endothelium-dependent relaxation, Acetylcholine, Spontaneously hypertensive rats
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