The aim of this study was to determine whether the KA value and fractional occupancy-response relationship for 5-hydroxytryptamine (5-HT) at 5-HT2A-receptors were altered in a rat model of genetic hypertension. Thus, the effects of phenoxybenzamine, an irreversible blocker at 5-HT2A-receptors, on the responses of the aorta from spontaneously hypertensive rats (SHRs) and normotensive rats to 5-HT have been examined. The two strains of normotensive rats used were Wistar Kyoto (WKY) rats and Wistar rats bred in Auckland (WA rats). 2. The sensitivity to 5-HT was increased in aortae from hypertensive rats. The pD2 values for 5-HT during the first challenge were 5.54 +/- 0.08 (14), 5.43 +/- 0.05 (12) and 6.08 +/- 0.04 (12) on the aorta of WKY rats, WA rats, and SHRs, respectively. 3. The affinity for 5-HT was increased in hypertension. Phenoxybenzamine at 2 x 10(-8)M for 30 min caused nonparallel rightward shifts of 5-HT response curves and the KA values were 16.8 x 10(-6)M, 45.6 x 10(-6)M and 4.4 x 10(-6)M on the WKY rat, WA rat, and SHR aorta, respectively. 4. There was a loss of receptor reserve for 5-HT in aortae from hypertensive rats. On the WKY and WA rat aortae, 5-HT caused 50 and 95% maximal responses by occupying 10-20 and 45-60%, whereas on the SHR aorta 5-HT produced 50 and 95% maximal responses by occupying 20-30 and 75-85% of the available 5-HT2A receptors, respectively. 5. The sensitivity to phenylephrine was not altered in hypertension. The mean pD2 values for phenylephrine were 7.14 +/- 0.05 (22) and 7.11 +/- 0.06 (22) on the WKY rat and SHR aorta, respectively. 6. These results show that there is a selective increase in sensitivity to 5-HT on the aorta in a rat model of genetic hypertension. There is also an increase in affinity for 5-HT at the 5-HT2A-receptors and a loss of 5-HT2A-receptor reserve for 5-HT responses on the aorta of SHRs.
