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

J Hypertens. 2003 Sep;21(9):1687-94. doi: 10.1097/00004872-200309000-00018.

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 AT(1) 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 AT(1) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Brain / enzymology*
  • Enalapril / pharmacology
  • Hydralazine / pharmacology
  • Hypertension / drug therapy
  • Hypertension / metabolism*
  • Hypertension / physiopathology*
  • Losartan / pharmacology
  • Male
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptor, Angiotensin, Type 1
  • Vasodilator Agents / pharmacology

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Receptor, Angiotensin, Type 1
  • Vasodilator Agents
  • Hydralazine
  • Enalapril
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Losartan