Effect of High Salt Intake in Mutant Mice Lacking Bradykinin-B 2 Receptors

Abstract

Renal kinins release prostaglandins and nitric oxide via the B 2 receptor, promoting diuresis and natriuresis; hence, they may also contribute significantly to blood pressure regulation. We hypothesized that mutant mice lacking the gene encoding for the bradykinin-B 2 receptor (B 2 -KO) become hypertensive when placed on a long-term high-salt diet. To test this, B 2 -KO and control mice were placed on either a normal (0.2%) or high-Na + diet (3.15% in food plus 1% saline as drinking water) for 8 weeks. Systolic blood pressure was determined during weeks 6 and 8 by a computerized tail-cuff system. At the end of the 8-week period, mice were anesthetized for determination of mean blood pressure, renal blood flow, and renal vascular resistance. In B 2 -KO mice maintained on high Na + , systolic blood pressure was 15 mm Hg higher than in knockout animals on normal Na + ( P <.01). In contrast, there was no difference in blood pressure in control mice fed either a normal or a high-Na + diet. Consistent with the systolic blood pressure data, direct mean arterial pressure revealed that B 2 -KO mice on high Na + were hypertensive (115±6 in B 2 -KO on high-Na + diet versus 79±2.8 in B 2 -KO on normal Na + , P <.0001); renal blood flow was reduced by 20% ( P <.05) and renal vascular resistance was doubled ( P <.0001) compared with B 2 -KO mice on normal Na + . In contrast, control mice on high Na + were normotensive and tended to have increased renal blood flow and decreased renal vascular resistance compared with control mice on a normal Na + diet. These findings indicate that kinins play an important role in preventing salt-sensitive hypertension; this may be achieved by maintaining renal blood flow under conditions of high salt intake.