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Prevention of vascular nitroglycerin tolerance by inhibition of protein kinase C
Author(s) -
Zierhut Wolfgang,
Ball Howard A.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15669.x
Subject(s) - staurosporine , protein kinase c , in vivo , medicine , pharmacology , aorta , blood pressure , chemistry , endocrinology , kinase , biology , biochemistry , microbiology and biotechnology
We investigated whether in vivo inhibition of protein kinase C (PKC) can prevent the development of vascular tolerance and restore the sensitivity of isolated vessels to nitroglycerin (NTG). Tolerance was induced in male Wistar rats by a constant i.v. infusion of NTG 1 mg kg −1 h −1 , a dose which did not alter blood pressure. After 72 h, the aorta was removed and the sensitivity of aortic rings to NTG tested. Chronic NTG infusion resulted in a 5.5 fold decrease in NTG‐sensitivity as compared with controls (vehicle), indicating the development of vascular tolerance. The simultaneous in vivo administration of the specific PKC inhibitor N‐benzoyl‐staurosporine (30 mg kg −1 day −1 ) prevented this decrease in NTG sensitivity. These results suggest a role for PKC activation in the development of vascular NTG tolerance.