Bradykinin B2-receptor blockade facilitates deoxycorticosterone-salt hypertension.
The contribution of endogenous kinins to the regulation of blood pressure, urinary volume, and renal sodium excretion was evaluated in Wistar rats on high sodium intake by using the new bradykinin receptor antagonist Hoe 140 (D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). Neither Hoe 140 (3 nmol/hr s.c. for 4 weeks) nor its vehicle altered systolic blood pressure (tail-cuff plethysmography) or renal function in rats given saline solution (0.15 mol/L NaCl) to drink ad libitum. Four-week administration of deoxycorticosterone (DOC), combined with high sodium intake and uninephrectomy, increased systolic blood pressure from 127 +/- 3 to 160 +/- 3 mm Hg (p < 0.01). When long-term infusion of Hoe 140 was combined with DOC, high sodium intake, and uninephrectomy, systolic blood pressure rose from 127 +/- 3 to 175 +/- 3 mm Hg (p < 0.01). The hypertensive effect was greater in the Hoe 140 group (48 +/- 4 versus 33 +/- 3 mm Hg in controls, p < 0.05). This difference was confirmed by direct measurement of mean blood pressure (Hoe 140 group, 154 +/- 4 mm Hg; vehicle group, 139 +/- 4 mm Hg; p < 0.05). The antagonist blunted the increase in urinary volume induced by salt load and DOC in uninephrectomized rats, whereas it did not alter the increase in urinary sodium excretion. These results suggest that endogenous kinins do not play a major role in the regulation of normal blood pressure in sodium-loaded rats, whereas they may attenuate the hypertensive effect induced by long-term administration of mineralocorticoids and salt in uninephrectomized rats.
Madeddu
P
P
Clinica Medica, Sassari University, Italy.
Parpaglia
P P
PP
Demontis
M P
MP
Varoni
M V
MV
Fattaccio
M C
MC
Tonolo
G
G
Troffa
C
C
Glorioso
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007610:Kallikreins / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D012965:Sodium Chloride / Q000494:pharmacology
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C065679:icatibant; D007610:Kallikreins; D001920:Bradykinin