Effects of NG‐nitro‐L‐arginine methyl ester on regional haemodynamic responses to MgSO4 in conscious rats

1 We assessed regional haemodynamic responses to the vasodilator, MgSO4, in the absence and presence of the nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), in conscious chronically instrumented Long Evans rats (n = 9). 2 MgSO4 (loading dose 220 μmol kg−1 min−1 for 7 min, maintenance dose 56 μmol kg−1 min−1 for 7 min), alone, caused slight bradycardia and hypotension accompanied by reductions in renal and mesenteric flows, but a marked hyperaemic vasodilatation in the hindquarters (flow, Δ 54 ± 6%, vascular conductance, Δ 77 ± 5%). 3 l-NAME (183 nmol kg−1 min−1) caused hypertension (29 ± 2 mmHg) accompanied by bradycardia (- 51 ± 6 beats min−1) and reductions in flow and vascular conductance in the renal (- 18 ± 4% and −35 ± 3%, respectively), mesenteric (- 35 ± 3% and −49 ± 3%, respectively), and hindquarters (- 26 ± 3% and −42 ± 3%, respectively) vascular beds. In the presence of l-NAME, the hypotensive and bradycardic effects of MgSO4 were still apparent, but its hindquarters hyperaemic vasodilator effect was significantly attenuated. 4 In order to determine if the inhibitory action of l-NAME on the hindquarters hyperaemic vasodilator action of MgSO4 was a non-specific effect, due to the change in baseline conditions caused by l-NAME, we also examined responses to MgSO4 in the presence of endothelin-1 (12.5 pmol kg−1 min−1) or angiotensin II (50 pmol kg−1 min−1). In the presence of either peptide, the overall effects of MgSO4 on hindquarters flow and vascular conductance were unchanged. 5 In a separate experiment (n = 8) we determined that the inhibitory effect of l-NAME on the hyperaemic vasodilator response to MgSO4 was prevented by l-arginine, and also demonstrated that the β2-adrenoceptor antagonist, ICI 118551, caused significant inhibition of the hindquarters haemodynamic effects of MgSO4. 6 We conclude that the hindquarters haemodynamic effects of MgSO4 in conscious rats involve a substantial l-NAME-sensitive component which depends on activation of β2-adrenoceptors, probably as a consequence of adrenal medullary adrenaline release.