Brain nitric oxide synthase activity in spontaneously hypertensive rats during the development of hypertension

Fatimunnisa Qadri*, Thomas Arens, Eike Christian Schwarz, Walter Häuser, Andreas Dendorfer, Peter Dominiak

*Corresponding author for this work
39 Citations (Scopus)

Abstract

Objectives: Blockade of neuronal nitric oxide synthase (nNOS) in the brain induced an increase in mean arterial pressure of spontaneously hypertensive rats (SHR). We hypothesize that increased nitric oxide (NO) synthesis in the brain compensates for hypertension. Therefore, we measured NOS activity in different brain regions in SHR at prehypertensive, onset and established hypertension, and compared with age-matched Wistar-Kyoto (WKY) rats. Method: NOS activity was measured by the ability of tissue homogenate to convert [ 3H]L-arginine to [3H]L-citrulline in a Ca2+- and NADPH-dependent manner. Results: NOS activity was impaired in the cerebral cortex and brainstem of prehypertensive SHR. At established hypertension, SHR showed an augmentation in NOS activity in hypothalamus and brainstem. Chronic treatment of SHR with the angiotensin-1 converting enzyme (ACE)-inhibitor, enalapril, and the AT1 receptor antagonist, losartan, normalized NOS activity in the hypothalamus but not in the brainstem. Treatment with a peripheral vasodilator, hydralazine, did not affect NOS activity. Conclusion: Attenuated NOS activity in the cortex and brainstem of prehypertensive SHR may play a role in the pathogenesis of hypertension. The upregulated NOS activity in the hypothalamus and brainstem of SHR possibly serves to compensate for hypertension. Hypothalamic, but not brainstem, NO is involved in antihypertensive effects of ACE inhibition and AT1 receptor blockade. Since a blood pressure decrease per se had no effect on NOS activity, it appears that central sympathetic activity influenced by endogenous angiotensin II, rather than blood pressure, represents the stimulus for the increased NOS activity in the hypothalamus of SHR.

Original languageEnglish
JournalJournal of Hypertension
Volume21
Issue number9
Pages (from-to)1687-1694
Number of pages8
ISSN0263-6352
DOIs
Publication statusPublished - 01.09.2003

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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