Contribution of the renin-angiotensin system to short-term blood pressure variability during blockade of nitric oxide synthesis in the rat

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 mu g kg(-1) min(-1), i.v., n = 10) and high-dose (100 mu g kg(-1) min(-1), i.v., n = 10) of L-NAME. The same treatment was applied in two further groups (2 x 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 (SEP) 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, SEP 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 SEP 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 mmHg(2) 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 SEP. 5 Losartan did not modify BP levels but had a tachycardic effect (+45 beats min(-1)). Moreover, losartan increased MF oscillations of SEP (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 SEP induced by L-NAME; the decrease of the MF oscillations of SEP induced by L-NAME was reinforced after losartan. 6 We conclude that the renin-angiotensin system is involved in the increase in variability of SEP 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.