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Effects of the antihypertensive agent, cicletanine, on noradrenaline release and vasoconstriction in perfused mesenteric artery of SHR
Author(s) -
Nasa Yoshihisa,
Yoshida Hiroyuki,
Urata Maki,
Uchibayashi Kumiko,
Tsunoda Yumi,
Kamigata Keiko,
Takeo Satoshi
Publication year - 1998
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 - 10.1038/sj.bjp.0701622
Subject(s) - vasoconstriction , phenylephrine , mesenteric arteries , medicine , vasoconstrictor agents , perfusion , endocrinology , blood pressure , vasodilation , pharmacology , artery , chemistry , anesthesia
The mechanism by which cicletanine (CIC) exerts its antihypertensive effects has not been fully elucidated. The present study was undertaken to examine the effects of in vivo and in vitro treatment with CIC on the pressor response and noradrenaline (NA) overflow during periarterial nerve stimulation (PNS) in perfused mesenteric arterial beds isolated from spontaneously hypertensive rats (SHR). CIC at a dose of 50 mg kg −1 day −1 was administered orally to both SHR and normotensive Wistar‐Kyoto rats (WKY) from the 6th to 10th week of age. At the 10th week, the isolated mesenteric arterial bed was perfused with Krebs‐Henseleit buffer and changes in perfusion pressure and NA overflow during PNS were measured. Chronic treatment with CIC suppressed the age‐related elevation of systemic blood pressure in SHR but not in WKY. The PNS (20 Hz)‐induced mesenteric vasoconstrictor response and NA overflow were greater in SHR than in WKY. In the vasculature of SHR chronic treatment with CIC resulted in a significant attenuation of the vasoconstriction and the NA overflow during PNS, whereas it did not alter vasoconstrictor responses to bolus injections of KCl and phenylephrine. Treatment with 30 μ M CIC in vitro diminished the PNS‐induced vasoconstriction and NA overflow but not the NA‐ and KCl‐induced vasoconstriction in the vasculature of untreated SHR. In the vasculature of SHR PNS‐induced NA overflow was attenuated by prostaglandin E 2 (0.05 μ M ), whereas it was augmented by the cyclo‐oxygenase inhibitor diclofenac‐Na (30 μ M ). In the presence of diclofenac, in vitro treatment with CIC did not attenuate the NA overflow during PNS. The results suggest that the antihypertensive effect of CIC in SHR is partially due to the presynaptic inhibition of NA release during sympathetic nerve activation. Transjunctional inhibition of NA release by prostaglandins may contribute to the inhibitory action of CIC on NA release in the vasculature of SHR.British Journal of Pharmacology (1998) 123 , 427–434; doi: 10.1038/sj.bjp.0701622