Korean J Physiol Pharmacol.  1998 Oct;2(5):573-580.

Altered cerebral vasomotion with decreased CGRP level in pial arteries of spontaneously hypertensive rats

Affiliations
  • 1Department of Pharmacology, College of Medicine, Pusan National University, Pusan 602-739, Korea.
  • 2Center for Biofunctional Molecules, Pohang University of Science and Technology, Pohang 790-600, Korea.

Abstract

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure (BP gtoreq 150 mmHg), and 4) SHR with normotensive BP (ltoreq 150 mmHg). The lower limit of CBF autoregulation in SHR shifted to a higher BP (82.8 +/- 9.3 mmHg, P < 0.05) than that in SDR (58.9 +/- 5.7 mmHg). In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin (3 X 10-7 M) was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were 12.5 +/- 1.4 and 9.8 +/- 2.8 fmole/mm2/60 min (P < 0.05), while those from SDR and WR were 25.5 +/- 3.1 and 24.6 +/- 3.1 fmole/mm2/60 min, respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

Keyword

Cerebral autoregulation; CGRP; Spontaneously hypertensive rats; Cerebral blood flow; Capsaicin
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