Doggrell Sheila A
Cardiovascular Pharmacology Group, Faculty of Medicine and Health Sciences, The University of Auckland, Private Bag 92109, Auckland, New Zealand.
J Pharm Pharmacol. 2002 Oct;54(10):1407-12. doi: 10.1211/002235702760345509.
There is a small increase in the functional beta2-adrenoceptor response on the spontaneously hypertensive rat (SHR) left atrium in the early stages of hypertension. In the present study, the functional beta1- and beta2-adrenoceptors of the left and right atrium in SHR pre-hypertension and age-matched (5-week-old) Wistar Kyoto (WKY) rats were characterized. Contractility methods with isoprenaline, T-0509 (a selective beta1-adrenoceptor agonist) and procaterol (a selective beta2-adrenoceptor agonist) were used. At 5 weeks, the SHRs were pre-hypertensive. Isoprenaline was more potent on the left atrium of 5-week-old SHRs than WKY rats. Bisoprolol, a selective beta1-adrenoceptor antagonist, was more potent against isoprenaline and T-0509 on the SHR than WKY rat left atrium. ICI 118,551, a selective beta(2)-adrenoceptor antagonist, was more potent against procaterol and T-0509 on the SHR than WKY rat left atrium. The results with bisoprolol and ICI 118,551 suggest that there are more functional beta(1)- and beta(2)-adrenoceptors on the left atrium of 5-week-old SHRs than WKY rats. Isoprenaline, T-0509 and procaterol were equipotent on the right atrium of 5-week-old WKY rats and SHRs. Bisoprolol was more potent against isoprenaline, T-0509 and procaterol on the SHR than WKY rat right atrium. ICI 118,551 was more potent against T-0509, but not isoprenaline and procaterol, on the SHR than WKY rat left atrium. This suggests there are more functional beta1-adrenoceptors, and probably more functional beta2-adrenoceptors, on the right atrium of 5-week-old SHRs than WKY rats. These functional differences in beta1- and beta2-adrenoceptor-mediated responses of the left and right atria of pre-hypertensive SHRs cannot be caused by hypertension, and may be associated with the onset of hypertension.
在高血压早期，自发性高血压大鼠（SHR）左心房的功能性β2 - 肾上腺素能受体反应有小幅增加。在本研究中，对高血压前期SHR以及年龄匹配（5周龄）的Wistar Kyoto（WKY）大鼠的左、右心房的功能性β1和β2 - 肾上腺素能受体进行了表征。采用了用异丙肾上腺素、T - 0509（一种选择性β1 - 肾上腺素能受体激动剂）和丙卡特罗（一种选择性β2 - 肾上腺素能受体激动剂）的收缩性方法。在5周龄时，SHR处于高血压前期。异丙肾上腺素对5周龄SHR左心房的作用比对WKY大鼠更强。比索洛尔，一种选择性β1 - 肾上腺素能受体拮抗剂，对SHR左心房上的异丙肾上腺素和T - 0509的拮抗作用比对WKY大鼠更强。ICI 118,551，一种选择性β2 - 肾上腺素能受体拮抗剂，对SHR左心房上的丙卡特罗和T - 0509的拮抗作用比对WKY大鼠更强。比索洛尔和ICI 118,551的结果表明，5周龄SHR左心房上的功能性β1和β2 - 肾上腺素能受体比WKY大鼠更多。异丙肾上腺素、T - 0509和丙卡特罗对5周龄WKY大鼠和SHR右心房的作用相当。比索洛尔对SHR右心房上的异丙肾上腺素、T - 0509和丙卡特罗的拮抗作用比对WKY大鼠更强。ICI 118,551对SHR左心房上的T - 0509的拮抗作用比对WKY大鼠更强，但对异丙肾上腺素和丙卡特罗无此作用。这表明5周龄SHR右心房上的功能性β1 - 肾上腺素能受体更多，可能功能性β2 - 肾上腺素能受体也更多。高血压前期SHR左、右心房β1和β2 - 肾上腺素能受体介导反应的这些功能差异并非由高血压引起，可能与高血压的发病有关。
