Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 281; no. 4; pp. H1778 - H1783
• Main Authors: Kintsurashvili, Ekaterina, Duka, Irena, Gavras, Irene, Johns, Conrado, Farmakiotis, Dimitrios, Gavras, Haralambos
• Format: Journal Article
• Language: English
• Published: United States 01.10.2001
• Subjects: Angiotensin II - pharmacology; Animals; Cells, Cultured; Gene Expression - drug effects; Heart - drug effects; Heart - physiology; Hemodynamics - drug effects; Male; Mice; Mice, Knockout - genetics; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Myocardium - cytology; Myocardium - metabolism; Rats; Rats, Wistar; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Receptors, Bradykinin - genetics; RNA, Messenger - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.281.4.H1778

Hypertension and Atherosclerosis Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 Bradykinin has vasodilatory and tissue-protective effects exerted via its B 2 type receptor, whereas the B 1 receptor is constitutively absent but inducible by inflammation and toxins. In previous studies, we found that B 2 receptor gene knockout mice exhibit overexpression of the B 1 receptor, which assumes a vasodilatory function and is further upgraded in renovascular hypertension. The present study was designed to explore the effects of excess angiotensin II (ANG II) on B 1 receptor and B 2 receptor gene expression in mouse cardiomyocytes and rat vascular smooth muscle cells (VSMC) in vivo (after a 3-day infusion of 30 ng/min ANG II in 11 wild-type and in 13 genetically engineered mice with deleted B 2 receptor gene) and in vitro (ANG II added in rat VSMC culture in the presence or absence of AT 1 or AT 2 receptor antagonist). Expression of B 1 and B 2 receptor mRNA was assessed by reverse transcriptase-polymerase chain reaction. ANG II infusion caused upregulation by 30% of the already significantly overexpressed B 1 receptors in cardiomyocytes of the B 2 receptor gene knockout mice, but in the wild-type mice it upregulated only the B 2 receptor mRNA by 47%. The addition of ANG II in VSMC culture produced a time-dependent induction of B 1 and upregulation of B 2 receptor gene expression, maximal at 3 h (by fivefold), declining almost to baseline by 24 h. The addition of losartan completely blocked this effect, whereas the AT 2 blocker PD-123319 made no difference, indicating that this is an AT 1 -mediated effect of ANG II. The data indicate that excess ANG II in subpressor doses in vivo upregulates expression of the B 2 receptor, but in its absence, the already overexpressed B 1 receptor is further upregulated, evidently assuming a counterregulatory response; in vitro, it transiently upregulates both bradykinin receptors. angiotensin infusion; B 2 gene knockout mice; cell culture