Loss of maximum attenuation and receptor reserve for isoprenaline at the beta2-adrenoceptors of the portal veins of hypertensive rats

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Objective:To test the hypothesis that vascular β2-adrenoceptor hyporesponsiveness in spontaneously hypertensive rats (SHR) is not induced by increased blood pressure or venous hypertrophy.Design:We compared the attenuating effects of isoprenaline, sodium nitroprusside and verapamil on the portal veins from Wistar-Kyoto (WKY) rats and SHR. We also studied the effects of slowly reversible β-adrenoceptor antagonists, bromoacetylalprenololmenthane (BAAM) and IC1147798, on the isoprenaline responses in order to determine the affinity and fractional β2-adrenoceptor occupancy-response relationships for isoprenaline.Results:The SHR portal veins did not develop hypertrophy. There was a small reduction in the sensitivity to isoprenaline and a marked reduction in the maximum attenuation of hypertension caused by isoprenaline. The sensitivity and efficacy of sodium nitroprusside and verapamil were not altered by hypertension. BAAM and IC1147798 inhibited the isoprenaline responses and reduced the maximum attenuation to isoprenaline. In the WKY rat portal vein the dissociation constant (KA) values for isoprenaline were independent of BAAM concentration, and was 1.78±0.32x10-7mol/l. Similar isoprenaline KA values were obtained from the ICM 47,798 data and in the SHR portal vein. In the WKY rat portal vein, from the BAAM data, it was calculated that isoprenaline produced 50, 95 and 100%maximum responses by occupying 6± 1, 20±3and 43±5% (n=21) of the available β2-adrenoceptors, respectively. Similar occupancy-response relationships were obtained in the WKY rat portal vein from the IC1147798 data. At each level of isoprenaline response the receptor reserve was significantly smaller in the SHR than it was in the WKY rat portal vein. Thus, from the BAAM data, isoprenaline produced 50, 95 and 100% maximum responses by occupying 14± 33±6 and 58±7% (n=15) of the available SHR portal vein β2-adrenoceptors, respectively.Conclusions:The SHR portal vein displays a selective β2-adrenoceptor hyporesponsiveness in the absence of a raised blood pressure or hypertrophy. This β2-adrenoceptor-associated hyporesponsiveness consisted of a marked loss of maximum attenuation in response to isoprenaline and of β2-adrenoceptor reserve for isoprenaline responses

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