Calcitonin gene-related peptide mediates the cardioprotective effects of rutaecarpine against ischaemia-reperfusion injury in spontaneously hypertensive rats.

摘要

1. It has been shown that calcitonin gene-related peptide (CGRP) plays an important role in mediating the cardioprotection exerted by rutaecarpine in normal animals. The aim of the present study was to determine whether rutaecarpine is able to decrease the susceptibility of hypertensive animals to ischaemia-reperfusion injury by stimulating CGRP release. 2. Spontaneously hypertensive rats (SHR) were pretreated with rutaecarpine (20 or 40 mg/kg per day, i.g.) for 18 days and then the heart and thoracic aorta were isolated for cardiac function and vascular relaxation analysis. Blood samples and coronary effluent were collected to measure CGRP levels and creatine kinase activity, respectively. The effect of 10 or 30 micromol/L rutaecarpine on CGRP release was also examined in isolated aortic rings set up in a homeothermal organ bath. 3. Rutaecarpine treatment resulted in a hypotensive effect in SHR concomitant with increases in plasma CGRP levels. In addition, rutaecarpine significantly stimulated the release of CGRP from aortic rings. Twenty minutes ischaemia and 30 min reperfusion resulted in a marked decrease in myocardial function and a significant increase in the release of creatine kinase in normal control (Wistar-Kyoto) rats, an effect that was exacerbated in SHR. Similarly, the decreased vasodilator response to acetylcholine (3 <--> 10(-9) to 10(-6) mol/L) in isolated aortic rings from Wistar-Kyoto rats was also aggravated in SHR. Both cardiac function and vasodilator responses were significantly improved in SHR after pretreatment with rutaecarpine. 4. The results of the present study suggest that the increased cardiac susceptibility to ischaemia-reperfusion injury in SHR is related to decreased plasma CGRP levels and that antihypertensive therapy with rutaecarpine reverses cardiac susceptibility to reperfusion injury by stimulating CGRP release.