Nitric oxide-dependent vasodilation and the regulation of arterial blood pressure

J Cardiovasc Pharmacol. 2001 Nov;38 Suppl 2:S19-22. doi: 10.1097/00005344-200111002-00006.

Abstract

Conflicting evidence has been reported on the hypothesis that vascular nitric oxide (NO) release is modulated by autonomic influences. Another controversial question is whether an insufficient degree of NO-dependent vasodilation may play a contributory role in the genesis of arterial hypertension. To address these questions we evaluated NO-dependent vasodilation in conscious rats subjected to various experimental manipulations that interfere with autonomic function: chronic chemical sympathectomy (CCSx), acute ganglionic blockade (AGx) and chronic sinoaortic denervation (CSAD). Experiments were also carried out on 6- and 12-week-old spontaneously hypertensive rats (SHR) (i.e. during the pre-hypertensive and the early established hypertensive stage) and in age-matched Wistar-Kyoto (WKY) rats. Nitric oxide-dependent vasodilation was quantified from the extent of blood pressure (BP) elevation in response to acute inhibition of NO synthesis by L-nitromonomethyl-L-arginine (L-NMMA). Chronic chemical sympathectomy was produced by repeated 6-hydroxydopamine injections; AGx was induced by hexamethonium infusion; and CSAD was obtained by aortic nerve section and carotid sinus wall stripping. Nitric oxide synthesis inhibition by L-NMMA was followed by a marked BP elevation in all groups. Rats with CCSx, Agx or CSAD never showed reduced BP responses to L-NMMA compared to intact, control rats. Neither 6- nor 12-week-old SHR had attenuated pressor responses to L-NMMA compared to age-matched WKY rats. In conclusion, the data indicate that (i) in unanaesthetized quietly-behaving rats there is no significant modulation of NO release by autonomic influences and (ii) young SHR have unimpaired NO-dependent vasodilation so it is unlikely that a deficit of vascular NO release plays any etiologic role in the BP elevation of this experimental model.

MeSH terms

  • Animals
  • Aorta / innervation
  • Blood Pressure / drug effects*
  • Chronic Disease
  • Denervation / methods
  • Ganglionic Blockers / pharmacology
  • Hexamethonium / pharmacology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sympathectomy / methods
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*
  • omega-N-Methylarginine / pharmacology*

Substances

  • Ganglionic Blockers
  • Vasodilator Agents
  • omega-N-Methylarginine
  • Nitric Oxide
  • Hexamethonium