beta-Adrenoceptor-mediated, nitric-oxide-dependent vasodilatation is abnormal in early hypertension: restoration by L-arginine.
BACKGROUND
It is unknown whether beta-adrenoceptor-mediated vasodilatation is altered in early hypertension and whether it can be modulated by L-arginine.


METHODS
We measured changes in forearm blood flow by plethysmography in response to acetylcholine (9 and 37 microg/min), sodium nitroprusside (200 and 800 ng/min) and the beta-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 micromol/min). In five individuals from each group, infusion of acetylcholine and isoproterenol was repeated during the concurrent blockade of nitric oxide synthesis by N-monomethyl-L-arginine (L-NMMA; 4 micromol/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 beta-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 beta-adrenoceptor responsiveness of smooth muscle cells. In this setting, supplementation of the nitric oxide precursor, L-arginine, enhances the vasodilator response to beta-adrenergic stimulation.
Schlaich
Markus P
MP
Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Australia. markus.schlaich@med4.med.uni-erlangen.de
Ahlers
Belinda A
BA
Parnell
Melinda M
MM
Kaye
David M
DM
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008499:Medical Records; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D000109:Acetylcholine