Effect of chronic exposure to cold on isoprenaline-induced cAMP accumulation and relaxation in the rat aorta.

ABSTRACT

Rats chronically exposed to cold (5 degrees C for 5 weeks) develop hypertension. Isoprenaline-induced vascular smooth muscle relaxation is increased in these animals. Our main objective was to compare isoprenaline-induced relaxation of aortae isolated from control and cold-acclimated rats and attempt to relate the differences to changes in receptor parameters (affinity and reserve) and signaling mechanisms. Isoprenaline (10(-9)-10(-5) M)-induced relaxation was enhanced significantly (p < 0.05) in aorta segments from cold-acclimated rats. There was a significant (p < 0.05) increase in the potency of isoprenaline but with no change in affinity. Isoprenaline produced 50% of the maximum response while occupying about 50% and about 15% of the receptors in isolated rat aorta segments from control and cold-treated rats, respectively. Forskolin and db-cAMP also concentration-dependently relaxed aorta segments from control and cold-acclimated rats. There was no difference in potency or maximum response to forskolin (which directly activates adenylyl cyclase) and db-cAMP. cAMP concentrations in the presence of isoprenaline were significantly (p < 0.05) higher in aorta segments from rats chronically exposed to cold when compared with aorta segments from control rats. These findings suggested that altered mechanisms upstream of activation of adenylyl cyclase are involved in the increased beta-adrenoceptor-induced relaxation.