Effect of acute inhibition of nitric oxide synthesis by l ‐NAME on cardiovascular responses following peripheral autonomic blockade in rabbits

The pressor and chronotropic responses to acute inhibition of nitric oxide synthase enzyme by N(G)-nitro-L-arginine methyl ester (L-NAME) were studied in anaesthetized rabbits with intact autonomic nervous system (ANS) activity. Also, they were investigated when administration of L-NAME was preceded by peripheral autonomic blockade. Autonomic blockade had different forms: ganglionic (hexamethonium-induced), post-ganglionic beta-adrenergic blockade (propranolol induced), parasympathetic blockade (atropine induced), and complete autonomic blockade by coadministration of hexamethonium and atropine simultaneously. L-NAME injected intravenously (10 mg/kg) in animals with intact and blocked autonomic activity induced a pressor response. This pressor response was accompanied by bradycardia in rabbits with either intact autonomic activity or hexamethonium-induced ganglionic blockade. L-NAME exerted no effect on heart rate in animals with beta-adrenergic blockade or parasympathetic blockade. In rabbits with complete autonomic blockade, L-NAME evoked tachycardia. These experiments indicate that L-NAME-induced hypertension is not relying only on ANS. Also, L-NAME-induced tachycardia in rabbits treated with atropine plus hexamethonium suggests other humoral mechanisms that may be involved in the L-NAME induced chronotropic response.