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 induced fluctuations of blood pressure, but it has proven difficult to separate their individual contributions because there is potential for interaction between the two. The present study was designed to examine the dynamics of the faster system during pharmacological blockade of tubuloglomerular feedback. Normotensive and hypertensive rats were studied under isoflurane or halothane anesthesia. Administration of the loop diuretic furosemide plus the angiotensin II (ANGII) AT1 receptor antagonist losartan caused a 10-fold or greater natriuresis, indicating profound inhibition of ascending limb salt transport, and also produced characteristic changes in the transfer function relating blood pressure (input) to renal blood flow (output). Operation of the 0.1-0.2 Hz mechanism was essentially unaltered, as shown by the presence of a peak in phase angle at 0.1-0.2 Hz and reduction of gain at frequencies slower 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 reduction below 0.05 Hz. Both during control and after inhibition of tubuloglomerular feedback, the 0.1-0.2 Hz system attenuated = 50% of the effects of spontaneous blood pressure fluctuations, suggesting that this mechanism, operating alone, can significantly stabilize renal blood flow in the face of spontaneous fluctuations of blood pressure.
Ajikobi
D O
DO
Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, QC, Canada.
Novak
P
P
Salevsky
F C
FC
Cupples
W A
WA
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004347:Drug Interactions; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004232:Diuretics; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D002034:Bumetanide; D000804:Angiotensin II; D005665:Furosemide; D007530:Isoflurane; D019808:Losartan; D006221:Halothane