title: Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats.
abstract: The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. The density of immunocytochemically stained nerve fibers in the mesenteric artery was quantified by computer-assisted image processing. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fivers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar Kyoto rats (WKY). The density of NPY-LI-containing sympathetic nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan) or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured by tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. However, the density after hydralazine treatment was similar to the level in non-treated SHR. The density of NPY-LI-containing nerve fibers was not increased by any of the drug treatments. These results suggest that long-term inhibition of the renin-angiotensin system in SHR prevents remodeling of CGRPergic nerve fibers and prevents the reduction of CGRPergic nerve function.
authors.affiliation: Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Hobara
authors.forename: Noriko
authors.initials: N
authors.lastname: Gessei-Tsutsumi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Goda
authors.forename: Fusako
authors.initials: F
authors.lastname: Takayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Akiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurosaki
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000375:Aging / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002452:Cell Count; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation*; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D009478:Neuropeptide Y; D013841:Thiazepines; D014665:Vasodilator Agents; D006830:Hydralazine; C055603:temocapril hydrochloride; D015740:Calcitonin Gene-Related Peptide; D019808:Losartan