title: Contribution of the renin-angiotensin and kallikrein-kinin systems to short-term variability of blood pressure in two-kidney, one-clip hypertensive rats.
abstract: Spectral analysis was recently chosen to characterize the fast oscillations, depending on the autonomic nervous system, in heart rate and blood pressure variabilities. Humoral stimuli could impinge on the low-frequency domain of blood pressure variability since the time lag to humoral 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 which the blood pressure level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and diastolic blood pressure and heart rate were computed in the high (respiratory)-, mid (0.2-0.6 Hz)- and low (0.02-0.2 Hz)-frequency bands, as detected by the fast Fourier transform technique in consecutive 102-s stationary periods. Hypertensive rats exhibited a marked low-frequency component of systolic (+261%) and diastolic (+169%) blood pressure variabilities when compared to sham-operated animals. First, losartan, a selective non-peptide angiotensin AT1 receptor antagonist, reduced this low-frequency component (-44% and -25% for systolic and diastolic blood pressure). In a second series of hypertensive rats, HOE 140, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, a bradykinin B2 receptor antagonist, decreased the low-frequency component of systolic (-28%) and diastolic (-40%) blood pressure. Losartan, added after HOE 140, induced a supplementary decrease of the low-frequency component (-60% and -42% for systolic and diastolic blood pressure). After the combined blockade, the low-frequency components of systolic and diastolic blood pressure variabilities of the hypertensive rats were equivalent to those of the control rats. Two-kidney, one-clip hypertension was also associated with an elevation of the mid-frequency component of the systolic blood pressure (+55%). The administration of HOE 140 did not change 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 pressure were increased by losartan in the two series of hypertensive rats. Losartan increased the mid-frequency component of heart rate variability in sham-operated rats while the heart rate variability was not modified during any of the treatment periods in two-kidney, one-clip rats. 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 kallikrein-kinin and the renin-angiotensin systems suggested the contribution of these humoral systems to this low-frequency component of blood pressure variability.
authors.affiliation: Laboratory of Pharmacology, CNRS URA 1482, Faculty of Medicine Necker-E.M., Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Ponchon
authors.forename: J L
authors.initials: JL
authors.lastname: Elghozi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D019808:Losartan; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D065168:Bradykinin Receptor Antagonists; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C065679:icatibant; D012083:Renin; D019808:Losartan; D001920:Bradykinin