BRADYKININ B2-RECEPTOR BLOCKADE FACILITATES DEOXYCORTICOSTERONE-SALT HYPERTENSION

The contribution of endogenous kinins to the regulation of blood press ure, urinary volume, and renal sodium excretion was evaluated in Wista r rats on high sodium intake by using the new bradykinin receptor anta gonist 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 blo od pressure (tail-cuff plethysmography) or renal function in rats give n saline solution (0.15 mol/L NaCl) to drink ad libitum. Four-week adm inistration of deoxycorticosterone (DOC), combined with high sodium in take 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 co mbined with DOC, high sodium intake, and uninephrectomy, systolic bloo d pressure rose from 127+/-3 to 175+/-3 mm Hg (p<0.01). The hypertensi ve 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 measure ment of mean blood pressure (Hoe 140 group, 154+/-4 mm Hg; vehicle gro up, 139+/-4 mm Hg; p<0.05). The antagonist blunted the increase in uri nary volume induced by salt load and DOC in uninephrectomized rats, wh ereas it did not alter the increase in urinary sodium excretion. These results suggest that endogenous kinins do not play a major role in th e regulation of normal blood pressure in sodium-loaded rats, whereas t hey may attenuate the hypertensive effect induced by long-term adminis tration of mineralocorticoids and salt in uninephrectomized rats.