Systemic nitric oxide clamping in normal humans guided by total peripheral resistance.
OBJECTIVE
We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels.


METHODS
Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography.


RESULTS
l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated.


CONCLUSIONS
Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.
Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense C, Denmark. jane.simonsen@ouh.regionsyddanmark.dk
J A
JA
Simonsen
M S
MS
Rasmussen
J B
JB
Johansen
P F
PF
Høilund-Carlsen
P
P
Bie
D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C026512:arginine methyl ester; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase