Effects of L-NMMA Acetate in DOCA-salt Hypertension

Introduction 

N^G-monomethyl-L-arginine (L-NMMA) acetate, a structural analogue of L-arginine, also named tilarginine acetate and methylarginine acetate, is a non-specific nitric oxide synthase (NOS) inhibitor which can provide inhibitory effects on all three NOS isoforms that are nNOS, eNOS, iNOS, respectively. L-NMMA acetate, with cell permeability and competitiveness, has been developed as a tool for studying the role and function of nitric oxide (NO) in a variety of diseases in vivo and in vitro such as high blood pressure, digestive system disease and so on.

Pharmacologic action

It is well recognized that the development of deoxycorticosterone acetate (DOCA)-salt hypertension has a close association with the sympathetic nervous system (SNS). The activation of SNS will result in a further increase of blood pressure. L-NMMA acetate has the ability to inhibit the formation of NO in the central nervous system by the inhibitory effect on NOS, which has been proved to activate the SNS. In other words, L-NMMA acetate has an augmented effect on the development of high blood pressure.

Function

L-NMMA acetate, as an effective tool for studying the effects of NO, has been involved in plenty of diseases mainly due to the inhibitory effect on NOS, as well as the formation of central NO. L-NMMA acetate is capable of inhibiting central NO formation to accelerate the development of DOCA-salt hypertension. In addition, L-NMMA acetate is able to reduce the vasodilation caused by Ginkgo biloba extract (GBE), owing to the inhibition of NO release in the endothelium and aortic vascular muscles.

Pharmacokinetics and metabolism

There are several kinds of administration forms available to inject L-NMMA acetate into body including intraperitoneal injection (IP), intracerebroventricular infusion (ICV) and some others. Chronic ICV of L-NMMA acetate exhibits a dose-dependent effect on DOCA-salt hypertension. The lower dose of L-NMMA acetate ICV gives a rise to blood pressure, while the higher dose has no influence on the hypertension. Research shows there is no effect on DOCA-salt hypertension with chronic IP of L-NMMA acetate.

References:

Ramchandra, R., Barrett, C. J., & Malpas, S. C. (2005). Nitric oxide and sympathetic nerve activity in the control of blood pressure. Clinical and Experimental Pharmacology and Physiology, 32(5‐6), 440-446.

Seto S, Nagao S, Ozeki S, et al. Contribution of central nitric oxide to the regulation of blood pressure and sodium balance in DOCA-salt hypertension[J]. Journal of Cardiovascular Pharmacology, 2006, 47(5):680-685.

Seto, S., Nagao, S., Ozeki, S. I., Tetsuo, H., Akahoshi, M., & Yano, K. (2006). Contribution of central nitric oxide to the regulation of blood pressure and sodium balance in DOCA-salt hypertension. Journal of cardiovascular pharmacology, 47(5), 680-685.

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