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(Hypertension. 2003;41:563.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR

From the Department of Medical Education and Research, Kaohsiung Veterans General Hospital (J.Y.H.C., L.L.W., Y.M.C.), and the Center for Neuroscience, National Sun Yat-sen University (S.H.H.C.), Kaohsiung, Taiwan, Republic of China.

Correspondence to Samuel H.H. Chan, PhD, Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, Republic of China. E-mail schan{at}mail.nsysu.edu.tw

We demonstrated recently that a significant reduction in both the molecular synthesis and functional expression of inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor outflow, underlies the augmented sympathetic vasomotor tone during hypertension. This study further evaluated the hypothesis that this downregulation of basal iNOS at the RVLM during hypertension is innate. In adult spontaneously hypertensive rats (SHR) treated for 4 weeks with the antihypertensive captopril to normalize elevated blood pressure or in young prehypertensive SHR, the significantly lower iNOS mRNA and protein levels at the ventrolateral medulla under basal conditions or on activation by microinjection bilaterally into the RVLM of lipopolysaccharide (10 ng) remained unaltered. The retarded efficacy of lipopolysaccharide (10 ng) to elicit cardiovascular depression (hypotension, bradycardia, and reduction in sympathetic vasomotor tone) also persevered in captopril-treated adult or young normotensive SHR. On the other hand, compared with Wistar-Kyoto normotensive rats, the magnitude of cardiovascular depression induced in adult SHR by local administration into the RVLM of the NO precursor L-arginine (40 nmol) was significantly smaller. In addition, microinjection bilaterally into the RVLM of a selective iNOS inhibitor, aminoguanidine (125 or 250 pmol), was discernibly less efficacious in unmasking hypertension, tachycardia, and the increase in sympathetic vasomotor tone in adult SHR. We conclude that a predisposed reduction in molecular synthesis and functional expression of basal iNOS in the RVLM is associated with the sympathetic vasomotor overactivity during hypertension.

Key Words: nitric oxide synthase • hypertension, essential • nitric oxide • blood pressure • heart rate • nervous system, autonomic

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