Hypertension due to chronic blockade of P1-purinoceptors

1. Long-term treatment of rats with 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), a non-selective antagonist of adenosine receptors, causes a hypertensive state. 2. In DPSPX-hypertensive rats, prejunctional alpha 2-adrenoceptors become supersensitive to the selective alpha 2-adrenoceptor agonist UK-14,304, while postjunctional adrenoceptor-mediated responses are not changed; furthermore, prejunctional beta-adrenoceptor-mediated facilitation of noradrenaline release is also enhanced. 3. In DPSPX-hypertensive rats, there are important morphological alterations of the small arteries, their lumina appearing strongly reduced and occasionally occluded by proliferation of the intimal cells. 4. In DPSPX-hypertensive rats, there is an increase in plasma renin, and captopril prevents not only the development of the hypertension but also the morphological changes in the arteries. 5. Other important changes occur in DPSPX-hypertensive rats: an alteration of the adrenergic regulation of the cardiac functions and an enhancement of perivascular neurotransmission. 6. These results suggest that adenosine may play an important role in the development of some kinds of human hypertension.