Biosynthesis of catecholamines and sympathetic outflow in spontaneously hypertensive rats (SHR) after chronic...

It has been reported that acute administration of captopril is followed by a decrease of norepinephrine (NE) release from the sympathetic nerves. Therefore, we studied the interactions between converting enzyme (CE) blocking agents and the presynaptic sympathetic nervous system after chronic administration of various CE inhibitors. Captopril, enalapril, and ramipril were administered orally to male spontaneously hypertensive rats (SHR) for 14 days. As parameters for catecholamine biosynthesis and storage, the activity of tyrosine hydroxylase and the catecholamine content of the hearts and the adrenal medulla were measured by high performance liquid chromotography (HPLC) in treated and control SHR. As an index of sympathetic outflow, plasma NE and epinephrine (E) levels were determined during preganglionic stimulation (PS) of the spinal cord. After chronic administration, no differences between the treated and control animals could be observed, either in the biosynthesis and storage of catecholamines in the heart and adrenal medulla or in the sympathetic outflow. However, after acute infusion of ramipril, a significant decrease in NE release was obtained. The dose-response curves of blood pressure vs. PS were significant shifted to the right when CE inhibitors were administered. It is suggested that the acute effect of CE inhibition on NE and E release (decreased sympathetic outflow) is blunted after long-term treatment with CE inhibitors because of increased angiotensin I (Ang I) and probably bradykinin. Both are capable of releasing NE and E at least from the adrenal medulla, like angiotensin II (Ang II).