Role of bradykinin B1 and B2 receptors in normal blood pressure regulation

• Published in: American journal of physiology: endocrinology and metabolism 2006-08, Vol.291 (2), p.E268-E274
• Main Authors: Duka, Arvi, Duka, Irena, Gao, Guohong, Shenouda, Sherene, Gavras, Irene, Gavras, Haralambos
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - physiology; Feedback - physiology; Gene Expression Regulation - physiology; Hemostasis - physiology; Male; Rats; Rats, Wistar; Receptor, Bradykinin B1 - metabolism; Receptor, Bradykinin B2 - metabolism; Reference Values
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00382.2005

Hypertension and Atherosclerosis Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts Submitted 16 August 2005 ; accepted in final form 14 February 2006 With inhibition or absence of the bradykinin B 2 receptor (B 2 R), B 1 R is upregulated and assumes some of the hemodynamic properties of B 2 R, indicating that both participate in the maintenance of normal vasoregulation or to development of hypertension. Herein we further evaluate the role of bradykinin in normal blood pressure (BP) regulation and its relationship with other vasoactive factors by selectively blocking its receptors. Six groups of Wistar rats were treated for 3 wk: one control group with vehicle alone, one with concurrent administration of B 1 R antagonist R-954 (70 µg·kg –1 ·day –1 ) and B 2 R antagonist HOE-140 (500 µg·kg –1 ·day –1 ), one with R-954 alone, one with HOE 140 alone, one with concurrent administration of both R-954 and HOE-140 plus the angiotensin antagonist losartan (5 mg·kg –1 ·day –1 ), and one with only losartan. BP was measured continuously by radiotelemetry. Only combined administration of B 1 R and B 2 R antagonists produced a significant BP increase from a baseline of 107–119 mmHg at end point, which could be partly prevented by losartan and was not associated with change in catecholamines, suggesting no involvement of the sympathoadrenal system. The impact of blockade of bradykinin on other vasoregulating systems was assessed by evaluating gene expression of different vasoactive factors. There was upregulation of the eNOS, AT 1 receptor, PGE 2 receptor, and tissue kallikrein genes in cardiac and renal tissues, more pronounced when both bradykinin receptors were blocked; significant downregulation of AT 2 receptor gene in renal tissues only; and no consistent changes in B 1 R and B 2 R genes in either tissue. The results indicate that both B 1 R and B 2 R contribute to the maintenance of normal BP, but one can compensate for inhibition of the other, and the chronic inhibition of both leads to significant upregulation in the genes of related vasoactive systems. bradykinin inhibition; angiotensin II; vasoactive factors; gene expression Address for reprint requests and other correspondence: H. Gavras, Chief, Hypertension and Atherosclerosis Section, Boston University School of Medicine, 715 Albany St., Boston, MA 02118 (e-mail: hgavras{at}bu.edu )