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

Abstract

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). 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%). 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. 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. 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. 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. 1994 British Pharmacological Society