Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ABSTRACT In the central nervous system, nitric oxide (NO) has been suggested to be a cell-to-cell signaling molecule that regulates guanylyl cyclase, aconitase, and iron regulatory protein. NO is also one of the substances that is involved in neuronal death. On the other hand, iron overload and enhanced hydroxyl radical formation have been implicated as the causative factors of some neurodegenerative disorders. The present study was performed to clarify whether nitric oxide is involved in iron-induced neuron death. Neurotoxicity was produced by microinjection of iron chloride (200 mM, 2.5 muL) into the left cerebral ventricle. After the intracerebroventricular (ICV) injection, all animals were kept alive for 10 days. During this period, animals in the iron + L-NAME (N-nitro-L-arginine methyl ester) and iron + aminoguanidine groups received intraperitoneal (IP) L-NAME (30 mg/kg) and aminoguanidine (100 mg/kg) injections once a day, respectively. Rats belonging to the control group also received intraperitoneally the same amount of saline. After 10 days, the rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using the standard histological techniques. The total numbers of neurons in substantia nigra of all rats were estimated with stereological techniques. It was found that L-NAME significantly decreased nigral cell loss from 43.2% to 14.0%, while aminoguanidine did not affect cell loss. Results of the present study suggest that NOS inhibition by L-NAME seems to have neuroprotective effects on iron-induced nigral neurotoxicity.
 ...
PMID:Role of nitric oxide synthesis inhibitors in iron-induced nigral neurotoxicity: a mechanistic exploration. 2002 Sep 5

Enhanced vasoconstriction and decreased vasodilatation due to endothelial dysfunction contribute to the progression of hypertension. Angiotensin (Ang)-(1-7) plays important roles in regulating the cardiovascular activity. The current study aimed to investigate the roles of Ang-(1-7) in modulating blood pressure, vascular tension and its signal pathway in spontaneously hypertensive rats (SHR). The effects of intravenous injection of drugs were determined in rats with anesthesia in vivo. Mesenteric artery (MA), coronary artery (CA) and pulmonary artery (PA) were isolated from rats and isometric tension measurements in arteries were performed. Compared with Wistar-Kyoto rats (WKY), the high K+ induced vasoconstriction was enhanced and acetylcholine-induced vasodilatation were attenuated in the MA, CA and PA in SHR. Intravenous injection of Ang-(1-7) decreased, while A-779 increased mean arterial pressure and abolished the hypotensive effect of Ang-(1-7) in SHR. Ang-(1-7) caused dose-dependent relaxation in MA, CA and PA in SHR, which was inhibited by pretreatment with Mas receptor antagonist A-779, nitric oxide (NO) synthase inhibitor l-NAME, guanylate cyclase inhibitor ODQ and protein kinase G (PKG) inhibitor DT-2. The Mas receptor expression, NO, cGMP and PKG levels of the three above arteries of SHR were lower than that of WKY. Ang-(1-7) increased the NO, cGMP and PKG levels in arteries from SHR, which was blocked by A-779. Activation of the Mas receptor by Ang-(1-7) relaxes the MA, CA, and PA through the NO-cGMP-PKG pathway, which contributes to the decrease of arterial pressure in SHR.
 ...
PMID:Angiotensin-(1-7) induced vascular relaxation in spontaneously hypertensive rats. 3088 Jan 6


<< Previous 1 2 3