CONTRIBUTION OF THE RENIN-ANGIOTENSIN AND KALLIKREIN-KININ SYSTEMS TOSHORT-TERM VARIABILITY OF BLOOD-PRESSURE IN 2-KIDNEY, ONE-CLIP HYPERTENSIVE RATS

Spectral analysis was recently chosen to characterize the fast oscilla tions, depending on the autonomic nervous system, in heart rate and bl ood pressure variabilities. Humoral stimuli could impinge on the low-f requency domain of blood pressure variability since the time lag to hu moral system activation is greater. This study was designed to analyse low-frequency components of short-term variability of blood pressure of conscious rats in conditions where humoral systems were activated. We studied rats with two-kidney, one-clip Goldblatt hypertension in wh ich the blood pressure level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and dias tolic blood pressure and heart rate were computed in the high (respira tory)-, mid (0.2-0.6 Hz)- and low (0.02-0.2 Hz)-frequency bands, as de fected by the fast Fourier transform technique in consecutive 102-s st ationary periods. Hypertensive rats exhibited a marked low-frequency c omponent of systolic (+261%) and diastolic (+169%) blood pressure vari abilities when compared to sham-operated animals. First, losartan, a s elective non-peptide angiotensin AT(1) receptor antagonist, reduced th is low-frequency component (-44% and -25% for systolic and diastolic b lood pressure). In a second series of hypertensive rats, HOE 140, D-Ar g-[Hyp(3),Thi(5),D-Tic(7), Oic(8)]bradykinin, a bradykinin B-2 recepto r antagonist, decreased the low-frequency component of systolic (-28%) and diastolic (-40%) blood pressure. Losartan, added after HOE 140, i nduced a supplementary decrease of the low-frequency component (-60% a nd -42% for systolic and diastolic blood pressure). After the combined blockade, the low-frequency components of systolic and diastolic bloo d pressure variabilities of the hypertensive rats were equivalent to t hose of the control rats. Two-kidney, one-clip hypertension was also a ssociated with an elevation of the mid-frequency component of the syst olic blood pressure (+55%). The administration of HOE 140 did not chan ge this component while losartan, alone or added after HOE 140, led to an increase (around +100%) in mid-frequency oscillations of systolic blood pressure. The high-frequency oscillations of systolic blood pres sure were increased by losartan in the two series of hypertensive rats . Losartan increased the mid-frequency component of heart rate variabi lity in sham-operated rats while the heart rate variability was not mo dified during any of the treatment periods in two-kidney, one-clip rat s. In conclusion, an increase in the low-frequency component of blood pressure variability was observed in a model of hypertension where the blood pressure is dependent upon humoral activities. The reduction of the slow fluctuations following the combined blockade of the kallikre in-kinin and the renin-angiotensin systems suggested the contribution of these humoral systems to this low-frequency component of blood pres sure variability.