Decreased CGRP level with increased sensitivity to CGRP in the pial arteries of spontaneously hypertensive rats.
It was aimed to investigate the importance of calcitonin gene-related peptide (CGRP) in maintenance of normal cerebral microcirculation. We examined both the functional (in vivo) and biochemical effects (in vitro) of CGRP on the pial arteries of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). When mock cerebrospinal fluid containing capsaicin (3 x 10(-7) M) was suffused over the cortical surface, the diameter of pial arteries of SHR was transiently increased and rapidly returned to the baseline level, while the capsaicin-induced increase in pial arterial diameters of WKY was large and sustained for a longer duration (> 10 min). Capsaicin-induced vasodilation was significantly attenuated by pretreatment with CGRP8-37, a CGRP1, receptor antagonist, in both WKY and SHR. On the other hand, cortical suffusion with CGRP (10(-9) approximately 10(-6) M) exerted a larger enhancement in the vasodilation of pial artery of SHR than WKY. The CGRP-induced vasodilation was significantly antagonized by CGRP8-37 in both WKY and SHR. The released level of CGRP-like immunoreactivity (CGRP-LI) from the pial artery was significantly lower in SHR (12.3 +/- 1.2 fmol/mm2/hr) than that in WKY (24.5 +/- 3.9 fmol/mm2/hr). CGRP (10(-6) M)-induced stimulation of cyclic AMP formation was rather larger in the pial arteries from SHR (50.2 +/- 5.8 fmol/mm2/30 min, p < 0.05) than those from WKY (34.5 +/- 3.8 fmol/mm2/30 min). These data suggest that, in the pial arteries of SHR, the transient vasodilation to capsaicin and enhanced vasodilation to CGRP are related to the decreased CGRP level in the cerebral microvascular beds, consequently leading to increased sensitivity of the CGRP receptors to CGRP.
Hong
K W
KW
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Yu
S S
SS
Shin
Y W
YW
Kim
C D
CD
Rhim
B Y
BY
Lee
W S
WS
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin