[Role of angiontensin receptors in remodeling perivascular nerves].
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. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fibers 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 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 using the 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. Furthermore, to clarify the effect of the angiontensin II type-2 (AT2) receptor in the restoration of perivascular nerve innervation, we used the phenol-injured rat model, in which the perivascular nerves are markedly reduced by the topical application of phenol. Activation of AT2R significantly restored CGRP-LI innervation in phenol-injured rats. These results suggest that selective stimulation of AT2 receptors facilitates reinnervation of mesenteric perivascular CGRP-containing nerves.
Department of Life Science, Okayama University of Science, Okayama, Japan. hobara@dls.ous.ac.jp
Narumi
N
Hobara
Mitsuhiro
M
Goda
Naoya
N
Hashikawa
Xin
X
Jin
Yoshito
Y
Zamami
Shingo
S
Takatori
Hiromu
H
Kawasaki
D000375:Aging / Q000378:metabolism / Q000473:pathology; 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; D019808:Losartan / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000294:innervation*; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009416:Nerve Regeneration; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013841:Thiazepines / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044139:Receptor, Angiotensin, Type 2; D013841:Thiazepines; C055603:temocapril hydrochloride; D015740:Calcitonin Gene-Related Peptide; D019808:Losartan