In vivo administration of D-arginine: effects on blood pressure and vascular function in angiotensin II-induced hypertensive rats.
OBJECTIVE
We tested the hypothesis that D-arginine (D-Arg), which is not a substrate for nitric oxide synthase but scavenges reactive oxygen in vitro, is protective in vivo.


METHODS
Rats were made hypertensive by administering angiotensin II (Ang II) (0.7mg kg(-1) per day) for 7 days (Ang II group). Two other groups additionally received either 3 mmol D-Arg (Ang II + D-Arg group) or vitamin C (1g) (Ang II + Vit C group) per day. Sham-operated animals served as controls (n = 6-9). Systolic blood pressure was monitored daily and cardiovascular function determined ex vivo at 7 days.


RESULTS
Ang II raised systolic blood pressure to 184mmHg, the increase was slightly attenuated by D-Arg treatment (-17mmHg; P < 0.05 versus Ang II alone) and prevented by Vit C. Acetylcholine-induced coronary relaxation was impaired in the Ang II group (P < 0.05 versus sham), the impairment was no different in the Ang II + D-Arg group, but prevented by Vit C. Likewise, Vit C but not D-Arg ameliorated reperfusion endothelium-dependent relaxation. However, in aortic rings D-Arg slightly improved acetylcholine relaxation (P < 0.05). Oxidative stress load estimated in plasma with thiobarbituric acid reactive substance was higher in the Ang II than the sham group, Vit C abolished the increase, but D-Arg was without effect.


CONCLUSIONS
D-Arg is weakly antihypertensive in vivo and ameliorates aortic, but not coronary endothelium-dependent relaxation ex vivo. Because D-Arg had no effect on plasma oxidant status, this protection appears to be independent of reactive oxygen scavenging activity.
Wölkart
Gerald
G
Institut für Pharmakologie und Toxikologie, Universität Graz, Universitätsplatz 2, A-8010 Graz, Austria.
Stessel
Heike
H
Brunner
Friedrich
F
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014655:Vascular Resistance
D000804:Angiotensin II; D001120:Arginine