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Contribution of the renin‐angiotensin system to short‐term blood pressure variability during blockade of nitric oxide synthesis in the rat
Author(s) -
Gouédard Olivier,
Blanc Jocelyne,
Gaudet Elisabeth,
Ponchon Pascal,
Elghozi JeanLuc
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16008.x
Subject(s) - losartan , renin–angiotensin system , blockade , nitric oxide , bradycardia , blood pressure , endocrinology , medicine , angiotensin ii , chemistry , bolus (digestion) , antagonist , receptor , heart rate
1 The aim of this study was to investigate, by use of spectral analysis, (1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L‐arginine analogue N G ‐nitro‐L‐arginine methyl ester (L‐NAME); (2) the involvement of the renin‐angiotensin system in these modifications, by use of the angiotensin II AT 1 ‐receptor antagonist losartan. 2 Blockade of NO synthesis was achieved by infusion for 1 h of a low‐dose (10 μg kg −1 min −1 , i.v., n = 10) and high‐dose (100 μg kg −1 min −1 , i.v., n = 10) of L‐NAME. The same treatment was applied in two further groups (2 × n = 10) after a bolus dose of losartan (10 mg kg −1 , i.v.). 3 Thirty minutes after the start of the infusion of low‐dose L‐NAME, systolic BP (SBP) increased (+ 10 ± 3 mmHg, P < 0.01), with the effect being more pronounced 5 min after the end of L‐NAME administration (+ 20 ± 4 mmHg, P < 0.001). With high‐dose L‐NAME, SBP increased immediately (5 min: + 8 ± 2 mmHg, P < 0.05) and reached a maximum after 40 min (+ 53 ± 4 mmHg, P < 0.001); a bradycardia was observed (60 min: −44 ± 13 beats min −1 , P < 0.01). 4 Low‐dose L‐NAME increased the low‐frequency component (LF: 0.02‐0.2 Hz) of SBP variability (50 min: 6.7 ± 1.7 mmHg 2 vs 3.4 ± 0.5 mmHg 2 , P < 0.05), whereas the high dose of L‐NAME not only increased the LF component (40 min: 11.7 ± 2 mmHg2 vs 2.7 ± 0.5 mmHg 2 , P < 0.001) but also decreased the mid frequency (MF: 0.2‐0.6 Hz) component (60 min: 1.14 ± 0.3 mmHg 2 vs 1.7 ± 0.1 mmHg 2 , P < 0.05) of SBP. 5 Losartan did not modify BP levels but had a tachycardic effect (+ 45 beats min −1 ). Moreover, losartan increased MF oscillations of SBP (4.26 ± 0.49 mmHg 2 vs 2.43 ± 0.25 mmHg 2 , P < 0.001), prevented the BP rise provoked by the low‐dose of L‐NAME and delayed the BP rise provoked by the high‐dose of L‐NAME. Losartan also prevented the amplification of the LF oscillations of SBP induced by L‐NAME; the decrease of the MF oscillations of SBP induced by L‐NAME was reinforced after losartan. 6 We conclude that the renin‐angiotensin system is involved in the increase in variability of SBP in the LF range which resulted from the withdrawal of the vasodilating influence of NO. We propose that NO may counterbalance LF oscillations provoked by the activity of the renin‐angiotensin system.