β-adrenoceptor-mediated, nitric-oxide-dependent vasodilatation is abnormal in early hypertension: Restoration by L-arginine

Background: It is unknown whether β-adrenoceptor-mediated vasodilatation is altered in early hypertension and whether it can be modulated by L-arginine. Methods and design: We measured changes in forearm blood flow by plethysmography in response to acetylcholine (9 and 37 μg/min), sodium nitroprusside (200 and 800 ng/min) and the β-receptor agonist, isoproterenol (50 and 200 ng/min) in 12 patients with essential hypertension (group EH) and in healthy volunteers with (group PFH; n = 14) and without (group NFH; n = 14) a family history of essential hypertension, before and during concomitant infusion of L-arginine (10 μmol/min). In five individuals from each group, infusion of acetylcholine and isoproterenol was repeated during the concurrent blockade of nitric oxide synthesis by N^G-monomethyl-L- arginine (L-NMMA; 4 μmol/min). Results: The response to acetylcholine was reduced in groups EH and PFH compared with group NFH (both P < 0.05), whereas the vasodilator effects of isoproterenol and sodium nitroprusside were similar in all three groups. Acetylcholine- and isoproterenol-induced vasodilatation did not change during infusion of the nitric oxide precursor, L-arginine, in group NFH, but were significantly enhanced by L-arginine in groups PFH and EH [forearm blood flow before and after isoproterenol 200 ng/min: group PFH 11.8 ± 1.02 and 13.3 ± 1.08 ml/min, respectively (P < 0.05); group EH: 11.3 ± 1.57 and 14.9 ± 1.91 ml/min, respectively (P < 0.01)]. Co-infusion of L-NMMA blunted the response to acetylcholine and isoproterenol in group NFH (P < 0.05), but did not significantly modify vasodilatation in groups PFH and EH. Conclusions: Although β-adrenergic vasodilatation seemed to be unaltered in early hypertension, L-arginine enhanced the response to isoproterenol, whereas concomitant inhibition of nitric oxide synthase by L-NMMA had no significant effect. These findings suggest that the nitric oxide component of isoproterenol-mediated vasodilatation is impaired in early hypertension and possibly compensated by increased β-adrenoceptor responsiveness of smooth muscle cells. In this setting, supplementation of the nitric oxide precursor, L-arginine, enhances the vasodilator response to β-adrenergic stimulation.