PHARMACOLOGICAL MODULATION OF SPONTANEOUS RENAL BLOOD-FLOW DYNAMICS

Two mechanisms contribute to renal autoregulation. The faster system, which is thought to be myogenic, operates at 0.1-0.2 Hz (i.e., 5-10 s/ cycle), while the slower one, tubuloglomerular feedback, operates at 0 .03-0.05 Hz (i.e., 20-30 s/cycle). Both attenuate spontaneous or induc ed fluctuations of blood pressure, but it has proven difficult to sepa rate their individual contributions because there is potential for int eraction between the two. The present study was designed to examine th e dynamics of the faster system during pharmacological blockade of tub uloglomerular feedback. Normotensive and hypertensive rats were studie d under isoflurane or halothane anesthesia. Administration of the loop diuretic furosemide plus the angiotensin II (ANGII) AT(1) receptor an tagonist losartan caused a IO-fold or greater natriuresis, indicating profound inhibition of ascending limb salt transport, and also produce d characteristic changes in the transfer function relating blood press ure (input) to renal brood flow (output). Operation of the 0.1-0.2 Hz mechanism was essentially unaltered, as shown by the presence of a pea k in phase angle at 0.1-0.2 Hz and reduction of gain at frequencies sl ower than 0.15 Hz. The 0.03-0.05 Hz mechanism was markedly inhibited, as shown by loss of the second phase angle peak at 0.03-0.05 Hz, loss of the local maximum in gain at 0.05 Hz, and loss of the second gain r eduction below 0.05 Pit. Both during control and after inhibition of t ubuloglomerular feedback, the 0.1-0.2 Hz system attenuated approximate to 50% of the effects of spontaneous blood pressure fluctuations, sug gesting that this mechanism, operating alone, can significantly stabil ize renal blood flow in the face of spontaneous fluctuations of blood pressure.