Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats

Abstract

Corticotropin-releasing factor (CRF) modifies cardiovascular function and hemodynamic status after administration into the central nervous system and into the peripheral circulation. The mechanisms by which CRF alters arterial pressure and heart rate have been examined in detail whereas little information exists regarding the processes mediating CRF-induced changes in regional blood flow. Therefore, studies were performed in conscious, unrestrained Sprague-Dawley rats to examine potential mechanisms underlying the regional hemodynamic effects of intracerebroventricular versus intravenous administration of CRF. Intracerebroventricular administration of CRF increased arterial pressure, heart rate, and mesenteric vascular resistance while decreasing iliac vascular resistance. Intravenous pretreatment with the CRF receptor antagonist, alpha-helical CRF9-41, did not alter the cardiovascular and hemodynamic responses to central administration of CRF. In contrast, prior ganglionic blockade prevented CRF-induced responses except for the reduction in iliac vascular resistance. Intravenous administration of CRF reduced arterial pressure and mesenteric vascular resistance, elevated heart rate, and transiently increased iliac vascular resistance. Intravenous pretreatment with alpha-helical CRF9-41 completely abolished the cardiovascular and hemodynamic responses to peripheral administration of CRF. Ganglionic blockade prior to intravenous administration of CRF augmented the reductions in arterial blood pressure and mesenteric vascular resistance, prevented the increase in heart rate, and unmasked a decrease in iliac vascular resistance. The divergent actions and mechanisms of action of CRF on regional hemodynamics when administered peripherally, as opposed to centrally, indicate that this peptide produces different hemodynamic effects that are specific to its site of action.