Sites at which clonidine acts to affect blood pressure and the secretion of renin, growth hormone and ACTH.

To further define the sites in the brain at which clonidine acts to lower blood pressure, inhibit renin secretion, inhibit ACTH secretion, and stimulate growth hormone secretion, small doses of this drug were infused into the vertebral arteries, into the carotid arteries and intravenously in pentobarbital-anesthetized dogs. Because injections of radioactive microspheres demonstrated that vertebral blood reached the hypothalamus, intravertebral and intracarotid infusions were also carried out after occlusion of the basilar artery in the midpontine region. Intracarotid clonidine, 2 microgram/kg, decreased plasma ACTH and corticoids and increased plasma growth hormone, whereas the same dose had no effect on these hormones when given intravenously or when given intravertebrally after occlusion of the basilar artery. Intravertebral clonidine lowered blood pressure to a greater degree than intracarotid and intravenous clonidine. The reduction in heart rate produced by clonidine was essentially the same whether the drug was administered via the intravenous, intracarotid, or intravertebral route. Intracarotid and intravertebral clonidine decreased plasma renin activity whereas in this dose intravenous clonidine did not. However, there was no renin response to intracarotid and intravertebral clonidine when the basilar artery was occluded. The data support the conclusion that clonidine acts rostral to the pons to decrease ACTH secretion and increase growth hormone secretion, whereas it acts on the medulla or adjacent hindbrain to lower blood pressure. In the dose used, clonidine appears to affect heart rate by a peripheral rather than a central action. The data confirm the observation that clonidine acts on the brain to inhibit renin secretion, and establish that the renin-inhibiting site is different from the blood pressure-lowering site. However, they do not permit localization of the renin-lowering site within the brain.