Inositolphosphate formation in thoracic and abdominal rat aorta following G(q/11)-coupled receptor stimulation

Although thoracic and abdominal rat aorta are often used as a classical pha rmacological preparation for the assessment of vascular drug effects, littl e is known on regional differences among these two parts of the aorta with regard to their reaction to G(q/11)-coupled receptor activation. Thus, we determined, in rings from thoracic and abdominal aorta from 12-wee k-old male Wistar rats, the effects of noradrenaline (NA; 10(-8)-10(-4) M), endothelin-1 (ET-1; 10(-10)-10(-6) M) and the thromboxane A(2) mimetic U 4 6619 (10(-8)-10(-5) M) on inositolphoshate (IP) formation (assessed as accu mulation of total [H-3]IPs in [H-3]myoinositol prelabelled rings). NA, ET-1 and U 46619 concentration-dependently increased IP formation; maximum incr eases were, however, significantly more pronounced in thoracic than in abdo minal aorta. Similarly, NA, ET-1 and U 46619 evoked significantly larger ma ximum contractions in thoracic than in abdominal aorta. NA-induced [H-3]IP formation could be inhibited with BMY 7378 (10(-9)-10(-4) M) and with 5-met hyl-urapidil (5-MU; 10(-9)-10(-5) M) both exhibiting biphasic concentration -inhibition curves. The pK(i)-values for BMY 7378 at the high affinity site were in thoracic aorta 8.93+/-0.28 (n=5), and in abdominal aorta 8.76+/-0. 35 (n=4) and at the low affinity site 6.45+/-0.2 (thoracic aorta) and 6.55/-0.27 (abdominal aorta). pK(i)-Values for 5-MU in thoracic aorta at the hi gh affinity site were 8.25+/-0.34 (n=4), and at the low affinity site 6.61/-0.39. In abdominal aorta reliable pK(i)-values could not be calculated fo r 5-MU due to a low signal-to-noise ratio. On the other hand, in both preparations the ETA-receptor antagonist BQ-123 (10(-9)-10(-5) M) and the TP-receptor antagonist SQ 29548 (10(-9)-10(-5) M) inhibited ET-1- and U 46619-induced IP formation, respectively, with monop hasic concentration-inhibition curves: pK(i)-values for BQ-123 were: 8.16+/ -0.24 (thoracic aorta) and 8.10+/-0.35 (abdominal aorta) and for SQ 29548: 8.2+/-0.3 (thoracic aorta) and 8.5+/-0.3 (abdominal aorta). The amount of i mmunodetectable G(q/11)-protein was similar in both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation and contra ctile force) are larger in thoracic than in abdominal aorta. ET-1 effects o n IP formation are mediated by ETA-receptors and U 46619 effects by TP-rece ptors. NA effects are mediated by alpha (1D)- and alpha (1A)-adrenoceptors; alpha (1B)-adrenoceptors seem to play a minor role.