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(Hypertension. 1997;29:483.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

Effect of High Salt Intake in Mutant Mice Lacking Bradykinin-B₂ Receptors

Marcos E. Alfie; David H. Sigmon; Silvia I. Pomposiello; Oscar A. Carretero

From the Hypertension and Vascular Research Division, Department of Medicine and Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich.

Correspondence to Oscar A. Carretero, MD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202

Renal kinins release prostaglandins and nitric oxide via the B₂ 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-B₂ receptor (B₂-KO) become hypertensive when placed on a long-term high-salt diet. To test this, B₂-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 B₂-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 B₂-KO mice on high Na⁺ were hypertensive (115±6 in B₂-KO on high-Na⁺ diet versus 79±2.8 in B₂-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 B₂-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.

Key Words: kallikrein-kinin system • bradykinin • bradykinin B₂ receptor knockout mouse • mean arterial pressure • renal blood flow • renal vascular resistance

Abbreviations: ACh = acetylcholine • B₂-KO = mouse with BK-B₂ receptor gene knocked out • BK = bradykinin • BP = blood pressure • MAP = mean arterial pressure • RBF = renal blood flow • RVR = renal vascular resistance • SBP = systolic BP

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