ALPHA(2)-ADRENOCEPTORS IN BRAIN AND KIDNEY DURING DEVELOPMENT OF HYPERTENSION IN DAHL-IWAI SALT-SENSITIVE RATS

Background: Both renal and extrarenal factors have been considered to contribute to the development of hypertension in Dahl salt-sensitive r ats, but contents of both factors have not been established precisely. Aim: To clarify the role of those factors in the sympathetic nervous system, we examined the regulation of alpha(2)-adrenoceptors in the lo wer brainstem and the renal tubular basolateral membranes simultaneous ly during the development of salt-induced hypertension in Dahl-Iwai sa lt-sensitive rats. Methods: Dahl-Iwai salt-sensitive or resistant rats were fed a high (8.0 % NaCl)- or low (0.3 %)- salt diet from 4 to 6 o r 10 weeks of age. At 4, 6 and 10 weeks of age, the plasma membranes o f the lower brainstem and the renal tubular basolateral membranes were obtained simultaneously and alpha(2)-adrenoceptors were quantified by a radioligand binding assay using H-3-rauwolscine. Results: In the sa lt-sensitive rats, systolic blood pressure was significantly higher in those fed a high-salt diet than in those fed a low-salt diet. In the salt-resistant rats, both the high- and the low-salt groups showed sim ilar blood pressure levels. At 6 weeks of age, alpha(2)-receptor densi ties of the salt-sensitive rats fed a high-salt diet were lower in the lower brainstem and higher in the renal basolateral membranes than th ose fed a low-salt diet. In contrast, in the salt-resistant rats, both the high- and the low-salt groups had similar densities. At 10 weeks of age, the difference between the high- and the low-salt groups in th e salt-sensitive rats disappeared in both the brainstem and the renal basolateral membranes. Conclusions: Alpha(2)-adrenoceptor regulation i n the brainstem and the renal basolateral membranes differs between Da hl-Iwai salt-sensitive and salt-resistant rats. The modulation of alph a(2)-adrenoceptors by a high salt intake may be essential particularly in the early phase of the development of salt-induced hypertension.