Local Renin-Angiotensin System in Sympathetic Overactivity of Spontaneously Hypertensive Rats

• Published in: Hypertension Research Vol. 19; no. 3; pp. 171 - 177
• Main Authors: Nagase, Miki, Shimosawa, Tatsuo, Ando, Katsuyuki, Fujita, Toshiro
• Format: Journal Article
• Language: English
• Published: England The Japanese Society of Hypertension 1996
• Subjects: angiotensin converting enzyme; angiotensin II; Angiotensin II - administration & dosage; Animals; AT1 receptor antagonist; Hypertension - metabolism; Hypertension - physiopathology; Male; Norepinephrine - metabolism; norepinephrine overflow; periarterial nerve stimulation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin-Angiotensin System; Sympathetic Nervous System - metabolism
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.19.171

The present study was designed to clarify whether modulation of norepinephrine (NE) release by vascular angiotensin (Ang) II is involved in the increased peripheral sympathetic activity of spontaneously hypertensive rats (SHR). In the perfusion system of isolated mesenteric vascular beds, periarterial nerve stimulation (PNS)-evoked NE overflow was significantly greater in SHR than Wistar-Kyoto rats (WKY). Administration of Ang II increased PNS-induced NE overflow, which could be reversed by pretreatment with the AT1 receptor antagonist CV-11974 in both types of rats; the facilitation by Ang II was more potent in SHR. Moreover, CV-11974 by itself could attenuate PNS-evoked NE overflow, the extent of which was also significantly greater in SHR, suggesting an augmented sympatho-facilitatory effect of enodogenous Ang II in SHR. Consistently, sympatho-facilitation by Ang I, which could be abolished by the angiotensin converting enzyme (ACE) inhibitor imidaprilat, was apparently greater than that of Ang II in SHR, despite no difference in WKY. These findings suggest that the increased peripheral sympathetic activity in SHR is attributed not only to the elevated sensitivity of nerve endings to Ang II but also to the increased local generation of Ang II, an effect possibly mediated by augmented vascular ACE activity. (Hypertens Res 1996; 19: 171-177)