Role of nitric oxide in modulating systemic pressor responses to different vasoconstrictors in man.
OBJECTIVE
Animal studies suggest that nitric oxide (NO) attenuates responses to endogenous vasoconstrictors. We investigated whether this also holds true in man by monitoring pressor responses to different vasoconstrictors during nitric oxide synthase (NOS) inhibition.


METHODS
Systemic hemodynamic responses to intravenous infusions of three doses (each for 5 min) of angiotensin II (AngII) (2, 4 and 8 ng/kg per min), noradrenaline (NOR) (10, 30 and 70 ng/kg per min) and phenylephrine (PE) (0.5, 1.0 and 1.5 microg/kg per min) were monitored in 44 healthy subjects during saline. A second dose-response curve was obtained during NOS inhibition with a subpressor dose of N- nitro-L-arginine-methyl ester (L-NAME) (5 microg/kg per min) or during a systemic NO clamp using combined systemic infusions of L-NAME (12.5 microg/kg per min) and nitroprusside. Blood pressure was measured in the brachial artery and other hemodynamic parameters were derived from this signal.


RESULTS
Mean arterial pressure (MAP) increased 2 +/- 2, 6 +/- 1 and 16 +/- 2 mmHg in response to AngII during saline, 7 +/- 6, 15 +/- 5 and 26 +/- 6 mmHg during the subpressor dose of L-NAME (P < 0.05) and 11 +/- 10, 18 +/- 7 and 25 +/- 6 mmHg during the systemic NO clamp (P < 0.001). These augmented responses of MAP were due to enhanced increments in systemic vascular resistance. Infusions of NOR and PE during saline resulted in dose-dependent increments in MAP and systemic vascular resistance. These increments were of comparable magnitude as those seen during AngII, but were not affected by NOS inhibition.


CONCLUSIONS
Our findings show that the systemic pressor response evoked by AngII, but not by NOR or PE, is enhanced during NOS inhibition, suggesting that AngII is associated with increased NO release that counteracts its blood pressure rising effect.
van der Linde
Nicole A J
NA
Erasmus MC, Department of Vascular and Metabolic Diseases, Rotterdam, The Netherlands. nvanderlinde@hotmail.com
Boomsma
Frans
F
van den Meiracker
Anton H
AH
D000328:Adult; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine