Kinin B1 and B2 receptor mRNA expression in the hypothalamus of spontaneously hypertensive rats.
The central hypertensive effects induced by bradykinin are known to be mediated via B2 receptors, which are present constitutively in the brain. B, receptors are rapidly upregulated during inflammation, hyperalgesia, and experimental diabetes. The hypothalamus plays an important role in the regulation of cardiovascular homeostasis, and all components of kallikrein-kinin system have been identified in this area. Therefore, we analyzed the mRNA expression of B1 and B2 receptors in the hypothalamus of spontaneously hypertensive rats (SHR) by RT-PCR. Male SHR were studied at three different ages corresponding to the three phases in the development of hypertension: (i) 3-4 (prehypertensive), (ii) 7-8 (onset of hypertension), and (iii) 12-13 weeks (established hypertension) after birth, and compared with age-matched Wistar-Kyoto (WKY) rats. At all ages tested, B2 receptor mRNA levels in the hypothalamus of SHR were higher than age-matched WKY rats (p < 0.001). However, the B1 receptor mRNA levels were higher at the established phase of hypertension only. We conclude that B1 and B2 receptor mRNA are differentially expressed in the hypothalamus of SHR and may play different roles in the pathogenesis of hypertension: upregulation of B2 receptor mRNA from early age may participate in the pathogenesis of hypertension, whereas an upregulation of B1 receptor mRNA in the established phase of hypertension may reflect an epiphenomenon in essential hypertension.
Qadri
F
F
Institute for Experimental and Clinical Pharmacology and Toxicology, University Clinic of Lübeck, Germany. qadri@medinf.mu-luebeck.de
Häuser
W
W
Jöhren
O
O
Dominiak
P
P
D000367:Age Factors; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000096:biosynthesis*
D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin