Influence of α₁and α₂-adrenoceptor antagonist therapy on the development of hypertension in spontaneously hypertensive rats

There is general agreement that the sympathetic nervous system is involved in the development of hypertension in spontaneously hypertensive rats (SHR). However, in a previous study we established that chronic administration of the selective α₁-adrenoceptor antagonist terazosin to SHR failed to prevent this phenomenon. In the present study, we extended that investigation further by examining the effects of another selective α₁antagonist (doxazosin), an α₂-adrenoceptor antagonist (yohimbine), and a combination of these agents. Chronic administration of doxazosin and yohimbine produced receptor blockade, as determined by their effect on blood pressure (BP) responses to norepinephrine (NE) and phenylephrine. Chronic administration of either antagonist alone or the two in combination failed to prevent the development of hypertension in SHR, however. These findings suggest that although there may be a need for involvement of the sympathetic nervous system in the development of hypertension in SHR, its influence on this process is not mediated through activation of α-adrenoceptors.