Chronic angiotensin II inhibition increases levels of calcitonin gene-related peptide mRNA of the dorsal root ganglia in spontaneously hypertensive rats.
We previously reported that the vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing nerves and level of CGRP mRNA in the dorsal root ganglia (DRG) in spontaneously hypertensive rats (SHR) decreased with age, and that the reduced function of CGRP nerves was restored by chronic inhibition of angiotensin II. The present study was performed to investigate the effect of long-term treatment with angiotensin II type-1 receptor antagonists (L-158,809 and olmesartan), an angiotensin converting enzyme inhibitor (temocapril) and hydralazine on levels of CGRP mRNA in DRG of SHR and the contents of CGRP in the mesenteric artery and atrium. The level of CGRP mRNA and degree of CGRP-like immunoreactivities (CGRP-LI) were measured by Northern blot hybridization assay and enzyme-linked immunosorbent assay, respectively. Seven week-treatment of 8 week-old SHR with temocapril (0.005%), L-158,809 (0.001%), olmesartan (0.01%) or hydralazine (0.01%) administered in drinking water significantly lowered the systolic blood pressure of SHR. The level of CGRP mRNA in the DRG of control SHR was significantly lower than that in normotensive Wistar Kyoto rats (WKY), whereas the level of CGRP-LI in the mesenteric artery and atrium of SHR were significantly greater than those in WKY. Treatment of SHR with temocapril, L-158,809, or olmesartan, but not hydralazine, significantly elevated the levels of CGRP mRNA in DRG, markedly increased the level of CGRP-LI in the mesenteric artery, and slightly increased the CGRP-LI level in the atrium. These results suggest that long-term inhibition of angiotensin II restores the reduced expression of CGRP mRNA in DRG and may facilitate neurotransmission of CGRP-containing vasodilator nerves in SHR.
Kawasaki
Hiromu
H
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama, Japan. kawasaki@pheasant.pharm.okayama-u.ac.jp
Inaizumi
Keiichi
K
Nakamura
Arisa
A
Hobara
Narumi
N
Kurosaki
Yuji
Y
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D000068557:Olmesartan Medoxomil; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D013841:Thiazepines; D000804:Angiotensin II; C070967:L 158809; D000068557:Olmesartan Medoxomil; C055603:temocapril hydrochloride; D015740:Calcitonin Gene-Related Peptide