Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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).
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PMID:Biosynthesis of catecholamines and sympathetic outflow in spontaneously hypertensive rats (SHR) after chronic treatment with CE blocking agents. 248 45

It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly used in the treatment of hypertension and chronic heart failure, have shown antioxidant properties in several tissues. Oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. In the present study, we treated rats with intraventricular injections of the dopaminergic neurotoxin 6-hydroxydopamine and subcutaneous injections of the angiotensin-converting enzyme inhibitor Captopril to study the possible neuroprotective effect of the latter on the dopaminergic system and on 6-hydroxydopamine-induced oxidative stress. Rats treated with Captopril and 6-hydroxydopamine showed significantly less reduction in the number of dopaminergic neurons (i.e., immunoreactive to tyrosine hydroxylase) in the substantia nigra and in the density of striatal dopaminergic terminals than 6-hydroxydopamine-lesioned rats not treated with Captopril. In addition, Captopril reduced the levels of major oxidative stress indicators (i.e., lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum of 6-hydroxydopamine-lesioned rats. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease and that further investigation should focus on the neuroprotective capacity of these compounds.
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PMID:Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of Parkinsonism. 1601 98