Responsiveness, affinity constants and beta 2-adrenoceptor reserves for isoprenaline on portal veins from normo- and pre- and hypertensive rats.
1. This study used contractility methods with the portal veins of 5- and 14-week-old Wistar-Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs). The SHRs are prehypertensive at 5 weeks. 2. The first part of our study was to determine whether the responsiveness to isoprenaline and forskolin was altered in the maturation of portal veins from normo- and prehypertensive rats. The responses to forskolin were similar on the portal veins of 5- and 14-week-old WKY and SHRs. 3. The sensitivity and maximum responses to isoprenaline were similar on portal veins of 5- and 14-week-old WKY. The sensitivity and maximum responses to isoprenaline were lower on the portal veins of 5-week-old SHRs (pD2 = 8.25, maximum = 85%) than age-matched WKY (pD2 = 8.79, maximum = 96%); these differences are not caused by hypertension. At 14 weeks, the sensitivity was similar (WKY pD2 = 8.74, SHR pD2 = 8.65) but the maximum responses to isoprenaline were lower on the portal veins SHRs (77%) than WKY (97%). Thus, the sensitivity to isoprenaline increases with the development of hypertension in the SHR portal vein. 4. The second part of the study was to determine whether the affinity for isoprenaline at beta2-adrenoceptors and the fractional beta2-adrenoceptor occupancy-response relationships on the portal vein were altered in maturation from normo- and pre-hypertensive rats. The effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor blocker, on the isoprenaline responses of 5- and 14-week-old WKY and SHRs were studied. Maturation of the WKY portal vein between 5 and 14 weeks was associated with a loss of affinity for isoprenaline (from pKA of 7.13 to 7.87), and increase in beta2-adrenoceptor reserve (from 72 to 92% at the 95% response). There were similar affinity and reserve findings in the maturation of the SHR portal vein. Thus, there are major changes in beta2-adrenoceptor structure and reserve in maturation on the portal vein that are irrespective of the development of hypertension.
Chen
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Cardiovascular Pharmacology Group, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Doggrell
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SA
D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011169:Portal Vein / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol