Acute cyclosporin A-treatment impairs the cytosolic guanylate cyclase-mediated vasodilatation in rat thoracic aorta.
- Author:
Hyun KOOK
1
Author Information
1. Department of Pharmacology, Chonnam University Medical School, 5 Hak-dong, Dong-ku, Kwansiu 501-190, South Korea.
- Publication Type:Original Article
- Keywords:
Cyclosporin A;
Cytosolic guanylate cyclase;
cGMP;
Vasodilatation;
Rat thoracic aorta
- MeSH:
Animals;
Aorta, Thoracic*;
Cyclosporine*;
Cytosol*;
Guanylate Cyclase;
Hypertension;
Nitroprusside;
Protein Kinase C;
Rats*;
Vasodilation*
- From:The Korean Journal of Physiology and Pharmacology
1998;2(4):471-477
- CountryRepublic of Korea
- Language:English
-
Abstract:
Cyclosporin A (CsA), a widely used immunosuppressant, is well known to cause nephrotoxicity and hypertension as major side effects. The present study was aimed at investigating the effects of CsA-pretreatment on the activities of cytosolic guanylate cyclase (cGC) in relation to the alteration of relaxant responses in the rat thoracic aorta. CsA (10 micrometer)-preincubation for 90 min significantly attenuated the vasodilatation induced by sodium nitroprusside (SNP), a cytosolic guanylate cyclase activator, shifting the dose-response curve to the right. The increase in cGMP contents induced by SNP was markedly attenuated by CsA. SNP (1 micrometer apprx 1 mM) increased the cGC activity dose-dependently, and the increase was completely abolished by CsA. CsA attenuated the SNP-induced cGC activation dose-dependently. The abolishing effect of CsA-pretreatment on the SNP-induced cGC activation was not affected by washing the preparation, suggesting that the inhibition is irreversible. When CsA was added simultaneously with SNP, cGC activation was not attenuated. 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H-7), a protein kinase C (PKC) inhibitor, decreased SNP-induced cGC activation and blocked the CsA-attenuation of cGC activation. These results suggest that CsA directly inhibits cGC participating in the CsA-induced impairment of vasodilatation, and that PKC is involved in the inhibitory action of CsA on cGC.
