Subarachnoid hemorrhage induced receptor upregulation in rat cerebral arteries.

Abstract

Objective The cerebral ischemia that occurs after a subarachnoid hemorrhage (SAH) often results in death or severe disability. Our hypothesis suggests that cerebral ischemia leads to pathophysiological endothelin (ET), 5-hydroxytryptamine (5-HT) and angiotensin (AngII) receptor changes in the vascular smooth muscle cells. Presently we wanted to study the time course for the upregulation of the receptors after SAH in cerebral arteries. Methods SAH was induced by injecting 250 μl blood into the prechiasmatic cistern. One, 3, 6, 12, 24 and 48 hrs after the SAH the basilar arteries (BA) and middle cerebral arteries (MCA) were harvested and contractile response to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and AngII were investigated with a myograph. ETA, ETB, 5-HT1B, AT1 and AT2 receptor mRNA levels were analyzed by quantitative real-time PCR. Results SAH resulted in enhanced contraction to ET-1 and 5-CT compared to fresh or sham rats. Ang II (via AT1 recpetors) induced increased contractile response (in the presence of the AT2 receptor antagonist PD123319). The contractile responses to ET-1, 5-CT and Ang II were successively increased with time, with a maximum at 48 hrs for 5-CT and ET-1 and 24 hrs for Ang II. In parallel the ETB, 5-HT1B, AT1 and AT2 receptor mRNA levels were elevated by time. Conclusion The results demonstrate that SAH induces upregulation of ETB, 5-HT1B, AT1 receptors in a time-dependent manner both at functional and mRNA levels. The study was supported by the Swedish Heart-Lung Foundation and the Lundbeck Foundation.