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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

L-NAME- and ADMA-induced sympathetic neural activation in conscious rats

¹Department of Internal Medicine, Division of Hypertension, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; and ²Department of Internal Medicine, Cardiovascular Center, University of Iowa, Iowa City, Iowa

Submitted 10 November 2004 ; accepted in final form 13 October 2005

Although studies in anesthetized, sino-aortic denervated animals indicate that inhibition of central nitric oxide (NO) causes an excitatory influence on efferent sympathetic nerve activity (SNA) that is normally offset by baroreflex activation, studies in conscious animals have not provided clear-cut evidence for a sympathoexcitatory effect of N-nitro-L-arginine methyl ester (L-NAME) or the endogenous circulating NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). Thus our goals were to 1) use surgical sino-aortic denervation to test for a sympathoexcititatory effect of intravenous L-NAME in conscious rats, and 2) to determine whether SNA responses to intravenous L-NAME can be extrapolated directly to intravenous ADMA. We recorded mean arterial blood pressure and renal SNA in both intact and sino-aortic-denervated conscious rats during 3 h of continuous intravenous infusion with either L-NAME or ADMA. When we eliminated the confounding influence of the sino-aortic baroreceptors, L-NAME produced a progressive increase in SNA with the peak response exceeding the baseline level of nerve firing by 150%. The same type of frank sympathetic activation was observed with intravenous ADMA. Taken together, these data offer straightforward evidence for L-NAME, as well as ADMA-induced sympathetic activation with direct recordings of SNA in conscious animals. These data confirm and extend the concept that circulating endogenous NOS inhibitors can constitute an excitatory signal to SNA.

baroreceptor reflex; neurogenic hypertension; sympathetic nervous system; sino-aortic denervation; asymmetric dimethylarginine

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