Peripheral cardiovascular effects in rats after central administration of histamine and antihistamines.

1. Vascularly isolated but nervously intact rat right hind limbs were perfused with blood at a constant flow rate and changes in perfusion pressure (proportional to vascular resistance), heart rate and blood pressure were monitored. 2. Histamine administered into the right lateral cerebral ventricle (i.c.v.) through guide cannulae, induced dose-dependent increases in perfusion pressure, heart rate and blood pressure. 3. Prior i.c.v. or i.v. administration of metiamide (an H2-antagonist) did not prevent the cardiovascular responses to i.c.v. histamine but rather prolonged them. Following i.c.v. or i.v. administration of chlorpheniramine (an H1-antagonist), however, changes in vascular resistance, heart rate and blood pressure were not significant. 4. Metiamide administration appeared to have some agonist activity on its own. Thus the role of H2-receptors in cardiovascular responses to centrally administered histamine remains unclear. 5. The work shows that in rats increases in nervous dishcarge to at least the hind limb vascular bed occur following central administration of histamine and conforms that increases occur in heart rate and blood pressure. These responses appear likely to be mediated through stimulation of central H1-receptors.