Vol. 284, Issue 2, 508-515, February 1998

Angiotensin Inhibits Neurotransmission of Calcitonin Gene-Related Peptide-Containing Vasodilator Nerves in Mesenteric Artery of Spontaneously Hypertensive Rats¹

Hiromu Kawasaki, Makoto Takenaga, Hiroaki Araki, Kojirou Futagami and Yutaka Gomita

Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Okayama University (H.K.), 1-1-1 Tsushimanaka, Okayama 700 and Department of Hospital Pharmacy, Okayama University Medical School (H.A., K.F., Y.G.), 2-5-1 Shikata-cho, Okayama 700 and the First Department of Internal Medicine, Miyazaki Medical College (M.K.), 5200 Kiyotake, Miyazaki 889-16, Japan

The role of angiotensin (Ang) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) (8- and 15-week-old) and age-matched Wistar Kyoto rats (WKY) was investigated. In both SHR and WKY preparations precontracted by continuous perfusion of Krebs' solution containing 7 µM methoxamine plus 5 µM guanethidine, periarterial nerve stimulation (PNS; 1 and 2 Hz) produced a frequency-dependent vasodilation, which was abolished by 100 nM tetrodotoxin and 500 nM CGRP(8-37) (CGRP receptor antagonist). The PNS-induced vasodilation in the SHR decreased with age and was smaller than that in the WKY. The neurogenic vasodilation in the SHR but not WKY was significantly inhibited by N-acetyltetradecapeptide renin substrate (RS, 100 and 500 nM), AngI (50 and 100 nM) and AngII (50 and 100 nM). The inhibitory effects of RS, AngI and AngII were abolished by the AngII receptor antagonist, [Sar¹,Ile⁸]AngII (500 nM). The effect of RS and AngI was inhibited by captopril (5 µM) and temocapril (500 nM). AngII (100 nM) had no effect on vasodilator response to exogenously infused CGRP (100 pmol). PNS (2 Hz) of perfused mesenteric vascular beds increased the release of CGRP-like immunoreactivities (CGRP-LI) in the perfusate, which was less in 15-week-old SHR than in age-matched WKY. AngII (100 nM) significantly inhibited the neurogenic release of CGRP-LI in the SHR but not in the WKY. These results suggest that exogenous and locally converted AngII, via AngII receptors, modulates the neurotransmission of CGRP-containing vasodilator nerves by inhibiting CGRP release from the nerve.