[Contribution of the renin-angiotensin system to the variability of blood pressure in hypertensive rat after blockade of nitric oxide synthesis].
The aim of this study was to investigate, using 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 L-NAME; 2) the involvement of the renin-angiotensin system in these modifications, using the angiotensin II AT1-receptor antagonist losartan. The blockade of the NO synthesis was made by infusion for 1 hour of a low dose (10 micrograms/kg/min, i.v.; n = 10) and a high dose (100 micrograms/kg/min, i.v.; n = 10) of L-NAME. The same treatment was applied in two further groups (n = 2 x 10) after a bolus of losartan (10 mg/kg, i.v.). The low dose of L-NAME increased systolic BP (SBP) on and after thirty min of infusion (+10 +/- 3 mmHg; p < 0.01). BP reached a maximum value 5 min after stopping L-NAME administration (+20 +/- 4 mmHg; p < 0.001). With the high dose of L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg; p < 0.05) and reached a maximum at 40 min (+53 +/- 4 mmHg; p < 0.001); a bradycardia was observed (60 min: -44 +/- 13 batt/min; p < 0.01). The low dose of L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2; p < 0.05). The high dose of L-NAME increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2; p < 0.001) and decreased the mid frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, p < 0.05) of SBP. Losartan did not modify BP levels but had a tachycardic effect (+33 +/- 10 batt/min; n = 27). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2; p < 0.001; n = 27). Losartan prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose. Losartan prevented the amplification of the LF oscillations of SBP induced by the L-NAME; the decrease of the MF oscillations of SBP induced by the L-NAME was reinforced after losartan). We concluded that the renin-angiotensin system is involved in the increase of variability of SBP in the LF range which resulted from the withdrawal of the vasodilatating influence of NO. We proposed that NO could counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.
Gouédard
O
O
Laboratoire de pharmacologie, CNRS URA 1482, faculté de médecine Necker-Enfants Malades, Paris.
Gaudet
E
E
Blanc
J
J
Ponchon
P
P
Elghozi
J L
JL
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester
Contribution du système rénine-angiotensine à la variabilité tensionnelle du rat hypertendu après blocage de la synthèse du monoxyde d'azote.