Effect of high salt intake in mutant mice lacking bradykinin-B2 receptors.
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.
Alfie
M E
ME
Department of Medicine, Henry Ford Hospital, Detroit, Micho 48202, USA.
Sigmon
D H
DH
Pomposiello
S I
SI
Carretero
O A
OA
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000172:deficiency* / Q000235:genetics; D012079:Renal Circulation / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D017673:Sodium Chloride, Dietary; D000109:Acetylcholine; D001920:Bradykinin