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Systemic nitric oxide clamping in normal humans guided by total peripheral resistance
Author(s) -
Simonsen J. A.,
Rasmussen M. S.,
Johansen J. B.,
HøilundCarlsen P. F.,
Bie P.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.02045.x
Subject(s) - sodium nitroprusside , nitric oxide , impedance cardiography , hemodynamics , vascular resistance , blood pressure , plasma renin activity , medicine , nitric oxide synthase , cardiac output , endocrinology , chemistry , anesthesia , heart rate , renin–angiotensin system , stroke volume
Aim: 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 ± 0.05 to 1.36 ± 0.07 mmHg s mL −1 , mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL −1 , P < 0.05). CO decreased with l ‐NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min −1 , P < 0.01) and returned to control when SNP was added (6.0 ± 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.