Stop-flow Pressure Feedback Responses Research Articles

Enhanced tubuloglomerular feedback in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

The present study was performed to evaluate tubuloglomerular feedback responses in transgenic rats [TGR(Cypa1a1Ren2)] with inducible malignant hypertension and to determine the degree to which feedback responsiveness is modulated by ANG II in these rats. Male Cyp1a1-Ren2 rats were fed a normal diet containing the aryl hydrocarbon indole-3-carbinol (I3C; 0.3%), for 5-6 days to stimulate expression of the Cyp1a1-Ren2 transgene and, thereby, to induce malignant hypertension. Stop-flow pressure (SFP) feedback responses to a late proximal perfusion rate of 40 nl/min were assessed in pentobarbital sodium-anesthetized rats during control conditions and after administration of the AT(1) receptor antagonist candesartan (0.1 mg/kg iv). Rats induced with I3C (n = 6) exhibited elevated mean arterial pressure and increased maximal SFP feedback responses compared with noninduced rats (n = 4; 163 +/- 4 vs. 130 +/- 2 mmHg, P < 0.01 and 16.3 +/- 1.4 vs. 11.7 +/- 0.5 mmHg, P < 0.05, respectively). Systemic candesartan decreased arterial pressure (to 98 +/- 7 and to 101 +/- 5 mmHg, respectively, P < 0.001) and attenuated SFP feedback responses (to 2.0 +/- 0.4 and to 3.3 +/- 0.9 mmHg, respectively, P < 0.01) in both hypertensive and normotensive rats. In additional experiments, peritubular capillary infusion of 10(-3) M candesartan did not alter arterial pressure but attenuated feedback responses in both hypertensive (19.3 +/- 1.4 to 8.8 +/- 0.9 mmHg, P < 0.01, n = 9) and normotensive Cyp1a1-Ren2 rats (9.0 +/- 0.8 to 4.7 +/- 0.6 mmHg, P < 0.01, n = 7). The present findings indicate that Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension exhibit augmented tubuloglomerular feedback responses. The data also show that AT(1) receptor activation by ANG II contributes to the enhanced feedback responsiveness in Cyp1a1-Ren2 rats with malignant hypertension.

Nitric oxide antagonizes the actions of angiotensin II to enhance tubuloglomerular feedback responsiveness

The present study was designed to investigate whether nitric oxide (NO) antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow pressure (SFP) responses to late proximal perfusion with artificial tubular fluid (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA) at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that did not decrease SFP under conditions of zero flow to the macula densa (resting SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and 16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M Ang II was associated with a tremendous increase in maximum TGF responses (23.8 +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest that local NO antagonizes Ang II with respect to the regulation of TGF responsiveness. Disruption of this balance by NO synthesis inhibition strongly potentiates TGF-independent and TGF-dependent actions of Ang II on the preglomerular vasculature.

Modulation of Tubuloglomerular Feedback by Angiotensin II Type 1 Receptors During the Development of Goldblatt Hypertension

It has been suggested that the increased levels of angiotensin II (Ang II) in the contralateral kidney of two-kidney, one clip (2K1C) Goldblatt hypertensive rats act to enhance tubuloglomerular feedback responsiveness and proximal tubular reabsorption and thereby exert a substantial sodium-retaining influence on the nonclipped kidney. The current study investigated the Ang II dependency of tubuloglomerular feedback responsiveness in the nonclipped kidney during the early stages of development of 2K1C hypertension. Stop-flow pressure feedback responses were assessed in the nonclipped kidney of 2K1C rats during control conditions and after systemic administration of the Ang II type 1 receptor antagonist losartan (10 mg/kg). In 1-week clipped and sham-operated rats, losartan administration decreased mean arterial pressure (from 143 +/- 6 to 123 +/- 2 mm Hg, P < .01, and from 129 +/- 2 to 106 +/- 5 mm Hg, P < .01, respectively) and attenuated the magnitude of the maximal feedback responses (from -12.9 +/- 1.2 to -3.0 +/- 0.3 mm Hg, P < .01, and from -13.2 +/- 1.5 to -3.6 +/- 1.1 mm Hg, P < .01, respectively). The decreases in mean arterial pressure were not significantly different in sham-operated and 1-week clipped rats. In 3-week clipped rats, mean arterial pressure was further elevated (163 +/- 6 mm Hg) compared with sham-operated rats (134 +/- 4 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

ANG II dependence of tubuloglomerular feedback responsiveness in hypertensive ren-2 transgenic rats.

The present study was performed to determine the angiotensin II (ANG II) dependence of stop-flow pressure (SFP) tubuloglomerular feedback responses in hypertensive transgenic rats [strain name: TGR(mRen2)27] harboring the mouse ren-2 renin gene. SFP feedback responses to increases in late proximal perfusion rate were assessed in pentobarbital-anesthetized male ren-2 transgenic rats during control conditions and after administration of the AT1 receptor antagonist, L-158,809 (1 mg/kg iv). During control conditions, increases in late proximal perfusion rate elicited flow-dependent decreases in SFP. The magnitude of the maximal SFP feedback response to a late proximal perfusion rate of 40 nl/min averaged 16.1 +/- 1.4 mmHg (n = 7), a value higher than that normally observed in normotensive rats. Administration of L-158,809 decreased mean arterial blood pressure (174 +/- 6 vs. 117 +/- mmHg, P < 0.01, n = 10) and attenuated the magnitude of the maximal SFP feedback response by 84 +/- 4% (16.1 +/- 1.4 vs. 2.6 +/- 0.5 mmHg, P < 0.01, n = 7). In contrast, mechanical reduction of renal arterial pressure from 179 +/- 5 to 113 +/- 1 mmHg (P < 0.01, n = 7) attenuated the magnitude of the maximal SFP feedback response by only 43 +/- 5% (14.4 +/- 1.9 vs. 7.9 +/- 0.7 mmHg, P < 0.01, n = 7), indicating that approximately one-half of the attenuation of SFP feed-back responses elicited by AT1 receptor blockade was due to removal of the stimulatory effect of ANG II on the sensitivity of the tubuloglomerular feedback mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Reabsorption of nitro-L-arginine infused into the late proximal tubule participates in modulation of TGF responsiveness

Previous studies indicate that endothelium-derived nitric oxide (NO) can directly modulate afferent arteriolar tone and that macula densa-derived NO can indirectly regulate afferent arteriolar tone by modulating the tubuloglomerular feedback (TGF) mechanism. The present in vivo micropuncture study evaluated whether the effect of late proximal tubular perfusion with the nitric oxide synthase (NOS) inhibitor, NG-L-arginine (NLA), on TGF responsiveness is related to reabsorption of NLA. Late proximal perfusion of 10(-3) M NLA resulted in a gradual, time-dependent enhancement of maximum TGF-mediated decreases in stop-flow pressure (SFP) from -7.1 +/- 0.7 to -19.4 +/- 1.6 mm Hg (P < 0.01). A detailed recording of SFP revealed that the maximum response during late proximal perfusion of NLA was obtained eight to nine minutes following the initiation of the perfusion, whereas maximum TGF responses evoked by late proximal perfusion with ATF were reached within one to two minutes. NLA infused into the late proximal segment of a neighboring nephron also resulted in enhancement of maximum SFP feedback responses from -5.5 +/- 0.5 to -10.4 +/- 1.9 mm Hg (P < 0.05), indicating that NLA can be reabsorbed and can consequently influence TGF responses. Finally, maximum SFP feedback responses were obtained prior to and following late proximal perfusion of 10(-3) M NLA dissolved in ATF, 10(-3) M NLA dissolved in 285 mM mannitol, and following perfusion with mannitol without NLA.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of tubuloglomerular feedback responsiveness by extracellular ATP

Experiments were performed in pentobarbital sodium-anesthetized rats to determine the effects of activation of P2 purinoceptors sensitive to ATP on glomerular capillary pressure, as estimated from proximal tubule stop-flow pressure (SFP) measurements, and on the magnitude of maximal tubuloglomerular feedback-mediated reductions in SFP. To selectively expose nephrons in vivo to ATP without influencing arterial blood pressure, we infused ATP directly into the surrounding peritubular capillaries. Peritubular capillary infusion, at a rate of 20 nl/min, of an isotonic saline solution containing 10(-3) M ATP elicited a transient decrease in resting SFP. However, subsequent infusion of 10(-3) M ATP together with the adenosine receptor (P1 purinoceptor) antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX, 10(-3) M) into the same vascular sites elicited a sustained decrease in resting SFP. Peritubular infusion of the slowly metabolizable ATP analogue, beta,gamma-methylene-ATP (10(-3) M), at a rate of 20 nl/min, also elicited a transient decrease in SFP, but this was not converted to a sustained response by PSPX. The SFP feedback responses to a late proximal perfusion rate of 40 nl/min were markedly attenuated during peritubular infusion of either 10(-3) M ATP (8.7 +/- 1.2 vs. 1.8 +/- 0.9 mmHg; P < 0.01, n = 9) or 10(-3) M beta,gamma-methylene-ATP (8.2 +/- 1.3 vs. 2.2 +/- 1.2 mmHg; P < 0.01, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers

Experiments were performed in pentobarbital-anesthetized rats to evaluate the dependence of the effector limb of the tubuloglomerular feedback mechanism on transmembrane calcium flux through potential-operated calcium channels. Peritubular capillary infusions of the calcium channel blockers, verapamil and nifedipine, were used to achieve high intrarenal levels without influencing arterial blood pressure. Proximal tubule stop-flow pressure (SFP) and single-nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses were obtained during control conditions and during simultaneous peritubular capillary infusion with an isotonic saline solution containing either verapamil or nifedipine. Infusion of either 10(-3) M verapamil or 10(-3) M nifedipine, at a rate of 20 nl/min, increased resting SFP (measured during conditions of zero distal volume delivery) and markedly attenuated both the SFP and SNGFR feedback responses to a late proximal perfusion rate of 30 nl/min. Infusion of verapamil (10(-3) M) also increased the slope of the relationship between SFP and renal arterial perfusion pressure between 80 and 120 mmHg (0.43 +/- 0.03 vs 0.24 +/- 0.02, P less than 0.001, n = 10). These findings support the hypothesis that the preglomerular contractile elements responsive to signals from the macula densa cells are activated by calcium influx through potential-operated calcium channels. Furthermore, the preglomerular contractile elements sensitive to calcium channel blockers can dilate further even when orthograde flow to a single macula densa segment is interrupted.

Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism.

To evaluate further the role of adenosine in the transmission of tubuloglomerular feedback signals, we studied the effects of an adenosine receptor antagonist and an adenosine A1-receptor agonist on feedback-mediated changes in stop-flow pressure (SFP). In orthograde perfusion experiments conducted in anesthetized rats, systemic administration of the adenosine receptor blocker 1,3-dipropyl-8-sulfophenylxanthine (PSPX) did not inhibit feedback responses. Control SFP feedback responses averaged 9.7 +/- 0.65 before and 8.6 +/- 0.55 mmHg during systemic infusion of the receptor blocker. In retrograde perfusion experiments, intratubular administration of the A1 agonist (360 nM) N6-cyclopentyladenosine (CPA), added to a hypotonic solution, markedly enhanced feedback responses. This effect was completely prevented by coinfusion of PSPX. Addition of 10 mM of the antagonist to the CPA-containing solution attenuated SFP feedback responses to less than 1 mmHg (delta = 0.44 +/- 0.50). Furthermore, PSPX also inhibited feedback responses obtained with an isotonic solution alone. Furosemide, which has been shown to block normal SFP responses obtained with isotonic solutions, failed to block CPA-induced decreases in SFP. These data demonstrate that intraluminal administration of an adenosine A1 analogue causes feedback-mediated decreases in SFP and therefore support a role for adenosine receptors in the signal transmission pathway.

Angiotensin influences on tubuloglomerular feedback mechanism in hypertensive rats

The tubuloglomerular feedback (TGF) mechanism was evaluated in the nonclipped kidney of Goldblatt hypertensive rats from both stop flow pressure (SFP) and single nephron glomerular filtration rate (SNGFR) responses to step increases in late proximal perfusion rate from 0 to 40 nl/min. During control conditions, increases in late proximal perfusion rate produced flow dependent decreases in SFP and SNGFR with maximal values of 10.2 +/- 1.0 mm Hg and 12.9 +/- 2.5 nl/min, values similar to those obtained in normal rats. During ACE inhibition (MK 422; 0.6 mg/kg/hr), arterial pressure decreased from 168 +/- 8 to 137 +/- 7 mm Hg and there was a marked attenuation in the magnitude of SFP feedback responses (delta = 2.5 +/- 0.3 mm Hg). SNGFR feedback responses, however, were not significantly impaired. Direct decreases in renal arterial pressure reduced control SFP but SFP feedback responses were maintained, indicating that the attenuated SFP feedback responses during ACE inhibition were not due to decreased arterial pressure. Superimposed infusion of angiotensin II during ACE inhibition partially restored SFP feedback responses. In contrast, norepinephrine infusion did not result in a similar restoration of SFP feedback sensitivity. These results indicate that the nonclipped kidney of Goldblatt hypertensive rats has an intact TGF mechanism as assessed from SFP and SNGFR feedback responses. Furthermore, ACE inhibition attenuates SFP but not SNGFR feedback responses, and systemic angiotensin II infusions can restore SFP feedback responsiveness towards normal.

Enhanced tubuloglomerular feedback during peritubular infusions of angiotensins I and II.

Experiments were performed in pentobarbital sodium-anesthetized rats to determine whether increases in intrarenal generation of angiotensin II (ANG II) can enhance the sensitivity of the tubuloglomerular feedback mechanism. Stop-flow pressure (SFP) feedback responses to step increases in late proximal perfusion rate were obtained during control conditions and during simultaneous peritubular capillary infusion of either angiotensin I (ANG I) or ANG II. Infusion of either 10(-7) M ANG II or 10(-5) M ANG I, at rates (18.3 +/- 0.9 and 14.8 +/- 1.5 nl/min, respectively) that did not affect resting SFP, enhanced the magnitude of SFP feedback responses both at a low proximal perfusion rate of 10 nl/min (2.9 +/- 0.9 vs. 0.3 +/- 0.2 and 4.5 +/- 1.0 vs. 0.1 +/- 0.1 mmHg, respectively) and at proximal perfusion rates (greater than 30 nl/min) that elicited a maximal feedback response (13.1 +/- 1.0 vs. 10.1 +/- 0.7 and 13.5 +/- 1.6 vs. 9.8 +/- 0.8 mmHg, respectively). With a higher ANG I infusion rate (20 nl/min), control SFP measured in the absence of distal volume delivery decreased from 39.2 +/- 0.6 to 12.0 +/- 2.8 mmHg (n = 18). These effects were blocked when the ANG II receptor antagonist, saralasin (10(-5) M, Sar), was added to the infusate. In addition, the magnitude of the maximal SFP feedback response was not altered during infusion of Sar alone or ANG I + Sar. These findings indicate that ANG II, either added or formed de novo beyond the glomerular circulation, can enhance the sensitivity of the tubuloglomerular feedback mechanism.

Evaluation of prostaglandins as mediators of tubuloglomerular feedback.

Orthograde and retrograde microperfusion experiments were conducted in Sprague-Dawley rats to evaluate the participation of vasoconstrictive eicosanoids as mediators of tubuloglomerular feedback (TGF) signals. Retrograde perfusion with 160 microM arachidonic acid (AA) added to a hypotonic solution enhanced the stop-flow pressure (SFP) feedback responses compared with those obtained with the control hypotonic solution (delta SFP, 1.6 +/- 0.4 vs. 10.1 +/- 0.7 mmHg with AA). Blockade of thromboxane A2 (TxA2) with the receptor blocker EP 092 or the synthesis inhibitor UK 38485 did not alter the magnitude of the SFP feedback responses obtained with an isotonic solution. Similarly, nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not alter maximal SFP feedback responses. Although indomethacin (5 mM) did induce attenuated SFP feedback responses (delta SFP, 9.5 +/- 0.7 vs. 0.5 +/- 0.4 mmHg with indomethacin), normal feedback responses were restored within 15-90 s after cessation of indomethacin perfusion. Additionally, SFP feedback responses were not inhibited with 5 mM piroxicam, a different cyclooxygenase inhibitor. These data fail to support a role for either TxA2 or lipoxygenase end products as mediators of TGF signals. The rapid restoration of feedback responses after indomethacin exposure and the lack of blockade with piroxicam suggest that transmission of feedback signals is not dependent on cyclooxygenase products.

Tubuloglomerular feedback responses in the rat during calmodulin inhibition.

Previously, we have suggested that a cytosolic calcium system participates in the transmission of signals between distal tubular fluid and the glomerular vascular elements. Since the Ca-binding protein calmodulin has been implicated in the intracellular actions of cytosolic Ca, we evaluated the effects of the calmodulin antagonists trifluoperazine (TFP) and calmidazolium (R24571) on tubuloglomerular feedback responses. In the rat, stop-flow pressure (SFP) was measured during retrograde perfusion into the distal tubule at 15 nl/min for 5 min. Perfusion with an isotonic Ringer solution resulted in a decrease in SFP of 12 +/- 1.1 mmHg (n = 34). With the addition of 50-75 microM TFP, SFP was decreased by 11 +/- 1.0 mmHg (n = 24); with 500 microM TFP, SFP feedback responses were 10 +/- 1.2 mmHg (n = 7). During perfusion with 20 microM R24571, SFP decreased by an average of 12 +/- 1.1 mmHg (n = 18). Single-nephron glomerular filtration rate feedback responses during retrograde microperfusion were also unaltered by R24571 (delta 15 +/- 2.5 vs. delta 14 +/- 2.6 nl/min). In the SFP experiments it was observed that the recovery of SFP toward preinfusion values after cessation of perfusion was significantly prolonged in tubules perfused with the calmodulin antagonists. SFP recovery times averaged 65 +/- 5.5 s (control), 104 +/- 9.9 s (50-75 microM TFP), 154 +/- 9.6 s (500 microM TFP), and 116 +/- 9.9 s (20 microM R24571). Accordingly, these results suggest that activation of calmodulin is not required for the transmission of tubuloglomerular feedback signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP-calcium interaction in the transmission of tubuloglomerular feedback signals

Recent studies have suggested that cytosolic calcium serves in the transmission of signals between distal tubular fluid and glomerular vascular elements. Since cAMP can modify calcium-mediated events, it was of interest to determine if agents that elevate intracellular cAMP could influence feedback responses and to assess the interaction of cAMP and intracellular calcium in the transmission of feedback signals. Stop flow pressure (SFP) was measured in the rat during retrograde microperfusion into the distal tubule at 15 nl/min. SFP averaged 37.5 +/- 0.5 mm Hg and decreased by 12.8 +/- 0.8 mm Hg (N = 44) during perfusion with an isotonic Ringer's solution. Addition of 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, decreased the magnitude of SFP feedback responses; 89 +/- 4.5% (N = 16) inhibition was observed at an IBMX concentration of 500 microM. In addition, SFP decreased by only 3 +/- 1 mm Hg (N = 8) during perfusion with 10 mM dibutyryl cAMP in the presence of a low concentration of IBMX and by 1.6 +/- 0.7 mm Hg (N = 12) during perfusion with forskolin, an agent that stimulates adenylate cyclase activity. Calcium ionophore (A23187) significantly increased the magnitude of SFP feedback responses obtained with IBMX alone from 5 +/- 1.0 mm Hg (N = 9; 250 micron IBMX) to 10 +/- 1.2 mm Hg (N = 11). These results indicate that agents which elevate intracellular cAMP markedly attenuate tubuloglomerular feedback responses and that calcium ionophore can reverse the inhibitory effects of increased cAMP.

Dissociation of tubuloglomerular feedback responses from distal tubular chloride concentration in the rat

Previous studies have demonstrated that stop-flow pressure (SFP) feedback responses can occur during orthograde perfusion with solutions having low amounts of sodium or chloride. However, retrograde perfusion studies have suggested a specific role for chloride concentration in mediating feedback responses. These studies were conducted to compare SFP feedback responses during orthograde and retrograde perfusion with an artificial tubular fluid solution (ATF) (Cl- = 135 meq/liter) and a Na+ isethionate solution (Cl- = 6 meq/liter). With ATF, increases in perfusion rate from 10 to 35 nl/min led to decreases in SFP of 11 +/- 1.4 mmHg, increases in distal tubular fluid Cl- of 46 +/- 4.9 meq/liter, and osmolality of 58 +/- 10 mosmol/kg. There were significant inverse relationships between SFP and changes in Cl- and osmolality. With Na+ isethionate, SFP decreased by 8.4 +/- 1.0 mmHg, osmolality increased by 43 +/- 8 mosmol/kg, and Cl- did not change. There was a significant relationship between SFP and osmolality, but not with Cl-. During retrograde perfusion at 15 nl/min, SFP decreased by 12 +/- 1.2 mmHg with ATF and by 12 +/- 1.2 mmHg with Na+ isethionate. These results demonstrate that feedback-mediated decreases in SFP can occur in the absence of concomitant increases in distal Cl- and suggest that the receptor system does not have a unique and specific requirement for chloride.

Stop-flow pressure feedback responses during reduced renal vascular resistance in the dog.

ARTICLESStop-flow pressure feedback responses during reduced renal vascular resistance in the dogP. D. Bell, and L. G. NavarP. D. Bell, and L. G. NavarPublished Online:01 Sep 1979https://doi.org/10.1152/ajprenal.1979.237.3.F204MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAngiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats16 November 2021 | Frontiers in Physiology, Vol. 12Renal Autoregulation in Health and DiseaseMattias Carlström, Christopher S. Wilcox, and William J. Arendshorst1 April 2015 | Physiological Reviews, Vol. 95, No. 2Direct assessment of tubuloglomerular feedback responsiveness in connexin 40-deficient miceMona Oppermann, Isabel Carota, Ina Schiessl, Christoph Eisner, Hayo Castrop, and Jurgen Schnermann1 May 2013 | American Journal of Physiology-Renal Physiology, Vol. 304, No. 9Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in miceJurgen Schnermann1 February 2011 | American Journal of Physiology-Renal Physiology, Vol. 300, No. 2 More from this issue > Volume 237Issue 3September 1979Pages F204-F209 Copyright & PermissionsCopyright © 1979 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.1979.237.3.F204PubMed474761History Published online 1 September 1979 Published in print 1 September 1979 Metrics

Influence of perfusate osmolality on stop-flow pressure feedback responses in the dog.

Influence of perfusate osmolality on stop-flow pressure feedback responses in the dog.

Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog.

Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.