title: Nitric oxide-dependent vasodilation and the regulation of arterial blood pressure.
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.
authors.affiliation: Medicina Interna I, Ospedale San Gerardo di Monza, Università di Milano-Bicocca, Milano, Italy. alberto.ferrari@unimib.it
authors.forename: A U
authors.initials: AU
authors.lastname: Ferrari
authors.forename: A
authors.initials: A
authors.lastname: Radaelli
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: L
authors.initials: L
authors.lastname: Mircoli
authors.forename: S
authors.initials: S
authors.lastname: Perlini
authors.forename: P
authors.initials: P
authors.lastname: Meregalli
authors.forename: L
authors.initials: L
authors.lastname: Fedele
authors.forename: G
authors.initials: G
authors.lastname: Mancia
mesh_terms: D000818:Animals; D001011:Aorta / Q000294:innervation; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D003714:Denervation / Q000379:methods; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013562:Sympathectomy / Q000379:methods; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D005730:Ganglionic Blockers; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D018738:Hexamethonium