Sympathetic vasoconstriction and renin secretion cause pressor responses to thyrotropin-releasing hormone in rats.

To study peripheral mechanisms underlying cardiovascular responses to thyrotropin-releasing hormone (TRH) we recorded the effects of i.c.v. infusions of TRH in urethane-anesthetized rats after various drug pretreatments, nephrectomy or renal denervation. TRH invariably increased blood pressure, heart rate and sympathetic nerve activity. After alpha-1 adrenergic blockade with prazosin, pressor responses to TRH were delayed in onset and reduced in magnitude. After renal denervation or pretreatment with propranolol for beta adrenergic blockade, captopril for converting enzyme inhibition or Sar1Ile8 angiotensin II for angiotensin II blockade, pressor responses to TRH were unaltered during the first few minutes but became significantly reduced thereafter. Bilateral nephrectomy inhibited markedly the whole pressor response including its onset and subsequent elevation. Consequently, initial inhibition by prazosin was considered due to removal of alpha-1 adrenergic vasoconstriction whereas the later attenuation was attributed to antagonism of the renin-angiotensin system. None of the procedures tested affected the attendant sympathetic hyperactivity, but the tachycardia was prevented by beta adrenergic blockade. These results are compatible with the interpretation that, by acting centrally, TRH stimulates sympathetic hyperactivity which then elevates blood pressure by increasing not only sympathetic vasomotor tone but also renal renin secretion.