Development of prejunctional alpha 2 adrenergic receptor mediated feedback control of the pressor response to sympathetic nerve stimulation in hypertensive and normotensive rats

Abstract

Development of prejunctional alpha 2 adrenergic receptor inhibition of pressor responses to sympathetic nerve stimulation in the spontaneously hypertensive Wistar-Kyoto rat was compared with genetically similar (Wistar-Kyoto) and different (Sprague-Dawley) normotensive rats. The sympathetic outflow was stimulated at frequencies of 1 to 20 Hz in pithed rats at 10,14,20 and 60 days of age. The antagonist, rauwolscine was given to block alpha 2 mediated feedback inhibition of noradrenaline release and the incidence of enhanced pressor responses determined. In Sprague-Dawley but not in spontaneously hypertensive or Wistar-Kyoto rats the changes in the incidence of enhanced responses parallel development of indices of sympathetic activity in other studies of the rat. Thus at 10 days of age (when activity is low), the incidence of rauwolscine-enhanced responses was 45%; at 14 days, (coinciding with onset of baroreflex control), incidence fell to 14%; in the 3rd postnatal week (when there is sympathetic hyperactivity), incidence increased to greater than 90%; finally, incidence, like activity declined in adults. In Wistar-Kyoto rats, the incidence of enhanced responses was like the other strains at 10 days but then decreased during development. In spontaneously hypertensive rats, enhanced responses were also less evident during week 3 and greatly diminished in adults. We conclude that in the spontaneously hypertensive and normotensive variants of Wistar-Kyoto strain rats the limit of alpha 2 adrenergic receptor feedback control of noradrenaline release is reached prematurely and is attenuated relative to the level of neuronal activity. In keeping with this hypothesis, the basal rate of noradrenaline utilization (measured in kidney) was higher at 20 days in Wistar-Kyoto than in Sprague-Dawley, but Sprague-Dawley showed greater enhancement of noradrenaline level and utilization after rauwolscine. Thus, the limitation to feedback control may be in development of prejunctional alpha 2 adrenergic receptors and/or their coupling to transmitter synthesis and release. Attenuated prejunctional alpha 2 adrenergic receptor inhibition is not linked obligatorily to development of hypertension in the spontaneously hypertensive Wistar-Kyoto rat.