Comparative regional haemodynamic effects of the nitric oxide synthase inhibitors, S ‐methyl‐ L ‐thiocitrulline and L ‐NAME, in conscious rats

The regional haemodynamic effects of the putative nNOS inhibitor, S ‐methyl‐ L ‐thiocitrulline (SMTC), were compared with those of the nonselective NOS inhibitor, N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME), in conscious, male Sprague–Dawley rats. SMTC (0.3 mg kg −1 bolus) produced a significant, short‐lived, pressor effect associated with renal, mesenteric and hindquarters vasoconstriction; the same dose of L ‐NAME did not affect mean blood pressure (BP), although it caused bradycardia and mesenteric vasoconstriction. At the highest dose tested (10 mg kg −1 ), L ‐NAME produced a significantly greater bradycardia and fall in mesenteric vascular conductance than SMTC, although the initial pressor response to SMTC was greater, but less sustained, than that to L ‐NAME. Infusion of SMTC or L ‐NAME (3 mg kg −1 h −1 ) induced rises in BP and falls in renal, mesenteric and hindquarters vascular conductances, but the effects of L ‐NAME were greater than those of SMTC, and L ‐NAME also caused bradycardia. The renal vasodilator response to acetylcholine was markedly attenuated by infusion of L ‐NAME, but unaffected by SMTC. The hindquarters vasodilatation induced by salbutamol was attenuated by L ‐NAME, but not by SMTC. The mesenteric vasodilator response to bradykinin was modestly enhanced by SMTC, but not by L ‐NAME. The depressor and renal, mesenteric and hindquarters vasodilator responses to sodium nitroprusside were enhanced by L ‐NAME, whereas SMTC modestly enhanced the hypotensive and renal vasodilator effects of sodium nitroprusside, but attenuated the accompanying tachycardia. The results are consistent with the cardiovascular effects of low doses of SMTC being attributable to nNOS inhibition.British Journal of Pharmacology (2003) 139 , 1235–1243. doi: 10.1038/sj.bjp.0705351