The interaction of endogenous opiates with autonomic circulatory control in the dog

The intravenous injection of either methionine or leucine enkephalin sharply reduces blood pressure, peak left ventricular pressure, and peak LV dP/dt in anesthetized dogs. The magnitude of the hypotensive response increases in proportion to the severity of the preceding surgical stress. The peptides are relatively ineffective after only simple surgical procedures but become highly effective when the autonomic balance is shifted toward sympathetic dependence after more complicated procedures or following bilateral carotid occlusion. The greater the animal's dependence upon sympathetic outflow to maintain blood pressure, the more effective is the opiate peptide. This suggests that the peripherally administered opiates may act by opposing existing adrenergic tone. Such antagonism of adrenergic tone during circulatory shock may help to explain some of the benefit of opiate receptor blockade in this condition. The rapid decline in blood pressure can be demonstrated in response to a variety of the proenkephalin-A derived peptides expected to circulate during physiological stresses. Based on a comparison of the responses to a series of peptides, the hypotensive effect is most likely mediated through activating opiate receptors of the delta subtype.