Dynamics and contribution of mechanisms mediating renal blood flow autoregulation

Abstract

-We investigated dynamic characteristics of renal blood flow (RBF) autoregulation and relative contribution of underlying mechanisms within the autoregulatory pressure range in rats. Renal arterial pressure (RAP) was reduced by suprarenal aortic constriction for 60 s and then rapidly released. Changes in renal vascular resistance (RVR) were assessed following rapid step reduction and RAP rise. In response to rise, RVR initially fell 5-10% and subsequently increased ϳ20%, reflecting 93% autoregulatory efficiency (AE). Within the initial 7-9 s, RVR rose to 55% of total response providing 37% AE, reaching maximum speed at 2.2 s. A secondary RVR increase began at 7-9 s and reached maximum speed at 10-15 s. Response times suggest that the initial RVR reflects the myogenic response and the secondary tubuloglomerular feedback (TGF). During TGF inhibition by furosemide, AE was 64%. The initial RVR rise was accelerated and enhanced, providing 49% AE, but it represented only 88% of total. The remaining 12% indicates a third regulatory component. The latter contributed up to 50% when the RAP increase began below the autoregulatory range. TGF augmentation by acetazolamide affected neither AE nor relative myogenic contribution. Diltiazem infusion markedly inhibited AE and the primary and secondary RVR increases but left a slow component. In response to RAP reduction, initial vasodilation constituted 73% of total response but was not affected by furosemide. The third component's contribution was 9%. Therefore, RBF autoregulation is primarily due to myogenic response and TGF, contributing 55% and 33-45% in response to RAP rise and 73% and 18-27% to RAP reduction. The data imply interaction between TGF and myogenic response affecting strength and speed of myogenic response during RAP rises. The data suggest a third regulatory system contributing Ͻ12% normally but up to 50% at low RAP; its nature awaits further investigation. renal circulation; afferent arteriole; glomerular arterioles; myogenic mechanism; tubuloglomerular feedback; vascular smooth muscle cells; macula densa cells; calcium channel blocker; furosemide; acetazolamide AUTOREGULATION OF RENAL blood flow (RBF) has been well characterized under steady-state conditions (2, 28, 36).Less is known about the dynamics and the relative contribution of the responsible mechanisms. Since the underlying mechanisms differ in their response times, the relative contributions affect the speed of overall regulation. Because of the continuous fluctuations of arterial pressure over a wide range of frequencies (33), the efficiency of autoregulation determines the size and range of pressure changes reaching glomeruli, peritubular capillaries, and medullary perfusion and will thus have an important bearing on fluid homeostasis and hypertensive renal damage.There is general agreement that renal autoregulation is mediated by at least two mechanisms, the tubuloglomerular feedback (TGF) and the myogenic response (36), and perhaps by a third (24). Although TGF participates, it appears that a d...

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

“…The myogenic response is much faster, with a natural frequency of 0.1-0.2 Hz in the anaesthetized rats and 0.2-0.3 Hz in conscious animals (2,32,36,38,56,76,122,165,166). Essentially similar data regarding the kinetics of these mechanisms have been obtained through analyses of RBF responses to step changes in BP (84,85,102,175). These natural frequencies imply that the myogenic response can prevent changes in RBF in response to BP fluctuations that occur at intervals greater than 3-4 s, whereas TGF responds to slower BP fluctuations over intervals of 20 s or longer.…”

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

“…Dynamic responses indicate that the secondary phase (between approximately 5 and approximately 25 s) is affected most markedly in mice lacking Cx40. This component has been shown to reflect the action of classical TGF in dogs, 29 rats, 30 and mice. 16 The present data therefore indicate that classical TGF is severely attenuated in the absence of Cx40.…”

“…The autoregulatory response of RBF to a rapid step increase in RAP within the autoregulatory pressure range was investigated as described previously. 16,27,30 The RAP increase was produced after reducing RAP 20 mmHg below the resting level for 60 to 70 s. This procedure was repeated every 5 min, thus allowing 4 min for recovery between RAP steps. Several steps were induced in each experimental period.…”

Exogenous 5′-nucleotidase improves glomerular autoregulation in Thy-1 nephritic rats

“…Although myogenic responses that are intrinsic to vascular smooth muscle cells are present in various vascular beds including cerebral, mesenteric, and coronary arteries (42), TGF is specific to the kidney (33). Recent analyses of renal autoregulation dynamics reveal that two mechanisms interact with each other (16). Because TGF constricts the terminal portion of the afferent arteriole, it increases upstream pressure, enhancing myogenic constriction and influencing the autoregulatory capacity of adjacent nephrons (17,37).…”