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Effects of losartan on short-term variability of blood pressure in SHR and WKY rats
E Gaudet1, J Blanc, J L Elghozi
1Laboratory of Pharmacology, CNRS URA 1482, Faculty of Medicine Necker-Enfants Malades, Paris, France.
Objective:
to examine the effect of losartan on short-term variability of blood pressure (BP) in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats.
Design And Methods:
variability of BP was characterized during baseline condition and 20 minutes after blocking the renin-angiotensin system (RAS) with the AT1 receptor antagonist losartan (10 mg/kg, iv). A Fast Fourier Transform algorithm was used for analysis.
Results:
under baseline conditions, SHR exhibited enhanced variability of BP compared to WKY, reflected by increased standard deviation (SD) of systolic BP (SBP). On the other hand, the mid frequency (0.2-0.6 Hz, MF) and the low frequency (0.02-0.2 Hz, LF) components of SBP were exaggerated. Enhanced MF area probably reflected a hyperactivity of the sympathetic nervous system in SHR. After a single injection of losartan, the mean BP was lowered in SHR by 13 +/- 5 mmHg, mean +/- SEM, P < 0.05). In WKY, losartan solely decreased the LF component of BP. In SHR, losartan increased the MF component of BP.
Conclusion:
losartan resulted in differential effects on BP variability in the two strains. In WKY, the RAS contributed to the genesis of LF fluctuations. In SHR, the increase in the MF component of BP after losartan probably indicated a reflex sympathetic activation triggered by vasodilation.