Endogenous Angiotensin II Modulates the Responsiveness of Renal Pelvic Mechanosensitive Neurons.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 680-680
Author(s):  
Ulla C Kopp ◽  
Lori A Smith
Keyword(s):  
Tap Water ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Deficient Diet ◽  
Renal Nerve ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Cox 2 ◽  
Pelvic Pressure

15 Increased (↑) renal pelvic pressure by increased urine flow rate or acute ureteral obstruction activates mechanosensitive neurons in the renal pelvic wall. Activation of these neurons increases ipsilateral afferent renal nerve activity (ARNA) and contralateral urinary sodium excretion (U Na V), i.e. a renorenal reflex. Activation of cyclooxygenase 2 (COX-2) contributes to the ARNA response to ↑ renal pelvic pressure. Since renal medullary COX-2 is upregulated by high Na + diet, we studied if the responsiveness of renal mechanosensitive neurons is altered by changes in dietary Na + . High Na + rats were placed on normal Na + diet and 0.9% NaCl to drink and low Na + rats on Na + deficient diet and tap water. ↑ renal pelvic pressure 2.5, 7.5 and 15 mmHg for 3 min increased ipsi ARNA 10±1%†, 21±2%† and 37±5%† in 6 high Na + rats and 1±0%, 10±0%† and 19±3%† in 5 low Na + diet rats (†p<0.05). The contra U Na V responses paralleled the ARNA responses, being 0.4±0.1, 1.1±0.3 and 1.4±0.5 μE/min/g in high Na + rats and 0±0, 0.1±0.1 and 0.2±0.1 μE/min/g in low Na + rats. Thus, the renorenal reflexes are suppressed by low Na + diet. Angiotensin (ANG) is increased by low Na + diet to facilitate Na + retention. Thus, we speculated that ANG would suppress the activation of the natriuretic renorenal reflexes in low Na + diet rats. Renal pelvic pressure was increased before and during renal pelvic perfusion with the AT1 receptor antagonist losartan, 200 μg/ml, in low Na + rats and before and during pelvic perfusion with ANGII, 15 nM, in high Na + rats. In 8 low Na + rats, losartan enhanced the ARNA responses to ↑ renal pelvic pressure 2.5 and 7.5 mmHg, ARNA responses being 2±1% and 14±1%‡ before and 13±2%‡ and 22±3%‡ during losartan. Conversely in 8 high Na + rats, ANGII suppressed the ARNA responses to ↑ renal pelvic pressure, ARNA responses being 10±1%‡ and 23±3%‡ before and 1±1% and 11±2%‡ during ANGII (‡p<0.01). Conclusion: Changes in dietary Na + modulate the responsiveness of the afferent renal nerves via the renin angiotensin system. Activation of the renorenal reflexes may contribute to increased U Na V during excess Na + intake. Of note, renorenal reflexes are impaired in SHR which are characterized by Na + retention.

Amiloride-sensitive Na+channels in pelvic uroepithelium involved in renal sensory receptor activation

1998 ◽  
Vol 275 (6) ◽  
pp. R1780-R1792 ◽  
Author(s):  
Ulla C. Kopp ◽  
Kazumichi Matsushita ◽  
Rita D. Sigmund ◽  
Lori A. Smith ◽  
Shigeru Watanabe ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Sensory Receptor ◽  
Renal Nerve ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Collecting Duct Cells ◽  
Pelvic Perfusion ◽  
Pelvic Pressure

Stretching the renal pelvic wall increases ipsilateral afferent renal nerve activity (ARNA). This response is enhanced by inhibiting Na+-K+-ATPase with ouabain, suggesting a modulatory role for intracellular Na+ in the activation of mechanosensitive neurons. The messenger RNA for α-, β-, and γ-subunits of epithelial Na+channels (ENaC) is found in collecting duct cells. Because ENaC subunits show homology with genes involved in mechanosensation, we examined whether ENaC mRNA could be found in the pelvic wall and whether the ARNA response to increased renal pelvic pressure was modulated by blockers of the Na+channel. α-, β-, and γ-subunits are present in the pelvis. The messenger RNA for the β- and γ-subunits is readily detected by in situ hybridization throughout the uroepithelium. The ARNA response to increased renal pelvic pressure was reduced by 53 ± 10% and 40 ± 10% ( P < 0.01) by renal pelvic perfusion with the inhibitors amiloride and benzamil, respectively. Amiloride inhibited the ouabain-induced enhancement of the ARNA response to increased renal pelvic pressure. The magnitude of this inhibition was inversely correlated with the magnitude of the amiloride-mediated blockade of the ARNA response to increased renal pelvic pressure ( P < 0.001). Amiloride also reduced the ARNA response to renal pelvic administration of substance P, a mediator of the ARNA response to increased renal pelvic pressure. We conclude that the ENaC complex in the pelvic uroepithelium participates in the activation of renal pelvic mechanosensitive neurons.

Do renal nerves chronically influence renal function and arterial pressure in spinal rats?

1992 ◽  
Vol 263 (6) ◽  
pp. R1265-R1270 ◽  
Author(s):  
K. A. Trostel ◽  
J. W. Osborn
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Cervical Spinal Cord ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Urine Ph ◽  
Renal Nerve ◽  
Renal Nerve Activity

Previous studies have demonstrated that renal nerve activity has acute effects on renal function in rats with cervical spinal cord transection (CST). The present study tested the hypothesis that renal nerves chronically influence renal and cardiovascular function in CST rats. Three groups of conscious Sprague-Dawley rats were studied: renal denervated plus CST (RDNX + CST), sham RDNX plus CST (sham + CST), and sham RDNX plus sham CST (intact). CST or sham CST surgeries were performed 8 days after RDNX or sham RDNX. Sodium and water intakes were fixed by intravenous infusion. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured before and for 9 days after CST/sham CST. In addition, urine flow, urinary sodium excretion, and urine pH were measured in the two groups of CST rats. One day after CST, MAP decreased approximately 25 mmHg in both RDNX + CST and sham + CST groups. PRA had fallen approximately 50% 1 day after CST and was not different between CST groups. PRA remained depressed throughout the study. There were no differences between sham + CST and RDNX + CST rats in any of the renal or cardiovascular variables measured after CST. In summary, we found no evidence for a chronic effect of renal nerves on renal function or arterial pressure in CST rats.

Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE2, and substance P

2000 ◽  
Vol 278 (4) ◽  
pp. R937-R946 ◽  
Author(s):  
Ulla C. Kopp ◽  
Donna M. Farley ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Substance P ◽  
Receptor Antagonist ◽  
Renal Nerve ◽  
Kinase C ◽  
Renal Nerve Activity ◽  
Substance P Receptor ◽  
Pelvic Perfusion ◽  
Pelvic Pressure

Increased renal pelvic pressure or bradykinin increases afferent renal nerve activity (ARNA) via PGE2-induced release of substance P. Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA response to bradykinin. We now examined whether bradykinin mediates the ARNA response to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked by renal pelvic perfusion with the bradykinin B2-receptor antagonist HOE 140 and the PKC inhibitor calphostin C by 76 ± 8% ( P < 0.02) and 81 ± 5% ( P < 0.01), respectively. Renal pelvic perfusion with 4β-phorbol 12,13-dibutyrate (PDBu) to activate PKC increased ARNA 27 ± 4% and renal pelvic release of PGE2 from 500 ± 59 to 1,113 ± 183 pg/min and substance P from 10 ± 2 to 30 ± 2 pg/min (all P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in ARNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mechanosensitive neurons by activating PKC. PKC increases ARNA via a PGE2-induced release of substance P.

Renal nerve effects on renal adaptation to changes in sodium intake during ovine pregnancy

1992 ◽  
Vol 262 (5) ◽  
pp. F823-F829
Author(s):  
G. W. Aberdeen ◽  
S. C. Cha ◽  
S. Mukaddam-Daher ◽  
B. S. Nuwayhid ◽  
E. W. Quillen
Keyword(s):  
Steady State ◽  
Sodium Intake ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Renal Nerve ◽  
High Sodium ◽  
Low Sodium ◽  
Pregnant Sheep ◽  
Urinary Potassium ◽  
Renal Nerve Activity

To assess the possibility of an enhanced role of renal nerves in the control of urinary sodium excretion (UNaV) and fluid homeostasis during pregnancy, urine output, UNaV, and urinary potassium excretion were assessed hourly for 3 days before and for 6 days after a step reduction in total daily sodium intake from 400 to 40 mmol. Studies were performed in normal conscious sheep (4 nonpregnant and 4 pregnant). Each animal was prepared with a divided bladder so that urine could be collected simultaneously from one normally innervated and one denervated kidney. In nonpregnant ewes, ratios of the rates of excretion by denervated vs. innervated kidneys for UNaV averaged 1.00 +/- 0.07 under steady-state conditions at high levels of sodium intake. This ratio was not different at the low-sodium-intake state. In contrast, this ratio was 1.15 +/- 0.07 at high sodium intake and 1.13 +/- 0.03 at low sodium intake in pregnant ewes. The ratios at both steady-state intake levels were different (P less than 0.05) between nonpregnant and pregnant sheep. During the transition between sodium intake states, these ratios were unchanged in nonpregnant animals, whereas pregnant animals exhibited peak ratios of 2.20 +/- 0.39 (P less than 0.05), indicating sodium wasting by the denervated kidneys. In summary, the data suggest that renal nerve activity may not be completely suppressed by high sodium intakes in pregnant sheep. Furthermore, the renal nerves have an enhanced influence on sodium conservation during and after the transition from high- to low-sodium-intake states during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory renorenal reflexes: a role for renal prostaglandins in activation of renal sensory receptors

1991 ◽  
Vol 261 (6) ◽  
pp. R1513-R1521 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith
Keyword(s):  
Chemical Activation ◽  
Urinary Sodium Excretion ◽  
Reflex Response ◽  
Sensory Receptor ◽  
Chemical Stimulus ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion

In anesthetized rats, activation of renal sensory receptors with a mechanical stimulus (increased ureteral pressure) and a chemical stimulus (renal pelvic perfusion with 0.9 M NaCl) results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion, i.e., a contralateral inhibitory renorenal reflex. Because both interventions are known to increase renal prostaglandin (PG) synthesis, we examined whether renal PGs were involved in the renorenal reflex response to renal sensory receptor stimulation. In the first part, mechanical and chemical activation of renal sensory receptors was performed in the absence and presence of renal pelvic perfusion with indomethacin or meclofenamate (0.2 micrograms/min). Indomethacin inhibited the ipsilateral afferent renal nerve activity response to increased ureteral pressure (7 +/- 2 vs. 38 +/- 10%, P less than 0.01) and renal pelvic perfusion with 0.9 M NaCl (3 +/- 3 vs. 28 +/- 5%, P less than 0.01) and the contralateral diuretic and natriuretic responses in the absence of any renal hemodynamic changes. Similar effects were produced by meclofenamate. In the second part, mechanical and chemical activation of renal sensory receptors was performed in the presence of renal pelvic perfusion with vehicle, indomethacin, and indomethacin plus PGE2 (20 micrograms/min). Addition of PGE2 to the renal pelvic perfusate in indomethacin-treated kidneys restored the responses to mechanical and chemical activation of renal sensory receptors to levels not different from their pre-indomethacin control values. We conclude that PGs in the renal pelvic area are involved in inhibitory renorenal reflex responses to mechanical and chemical activation of renal sensory receptors.

scholarly journals Activation of endothelin A receptors contributes to impaired responsiveness of renal mechanosensory nerves in congestive heart failureThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (6) ◽  
pp. 622-629 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Susan Y. Jones
Keyword(s):  
Substance P ◽  
Sensory Nerve ◽  
Reflex Response ◽  
Nerve Activity ◽  
Renal Nerve ◽  
P Release ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Substance P Release ◽  
Pelvic Pressure

Increasing renal pelvic pressure results in PGE2-mediated release of substance P, leading to increases in afferent renal nerve activity (ARNA) and natriuresis, that is, a renorenal reflex response. The renorenal reflexes are impaired in congestive heart failure (CHF). Impairment of the renorenal reflexes may contribute to the increased renal sympathetic nerve activity and sodium retention in CHF. Endothelin (ET)-1 contributes to the pathological changes in cardiac and renal function in CHF. Therefore, we examined whether the ETA receptor antagonist BQ123 altered the responsiveness of renal mechanosensory nerves in CHF. The ARNA responses to increasing renal pelvic pressure were suppressed in CHF but not in sham-CHF rats. In CHF, increasing renal pelvic pressure by 7.5 mm Hg before and during renal pelvic perfusion with BQ123 increased ARNA 12% ± 3% and 21% ± 3% (p < 0.05 vs. vehicle). In isolated renal pelvises from CHF rats, PGE2 increased substance P release from 5 ± 0 to 7 ± 1 pg/min without BQ123 and from 4 ± 1 to 9 ± 1 pg/min with BQ123 in the bath (p < 0.01 vs. vehicle). BQ123 had no effect on the ARNA responses or substance P release in sham-CHF. In conclusion, activation of ETA receptors contributes to the impaired responsiveness of renal mechanosensory nerves in CHF rats by a mechanism(s) at the renal sensory nerve endings.

Role of prostaglandins in renal sensory receptor activation by substance P and bradykinin

1993 ◽  
Vol 265 (3) ◽  
pp. R544-R551 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith
Keyword(s):  
Substance P ◽  
Urinary Sodium Excretion ◽  
Receptor Activation ◽  
Prostaglandin Synthesis ◽  
Sensory Receptor ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion

In anesthetized rats increasing ureteral pressure results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion that is dependent on intact prostaglandin synthesis. Activation of renal pelvic substance P receptors contributes to the renorenal reflex responses to increased ureteral pressure. Because these data suggested that renal sensory receptors could be activated by both prostaglandins and substance P we examined whether activation of renal sensory receptors by substance P was dependent on intact prostaglandin synthesis. The renal pelvis was perfused with capsaicin, 2.5 micrograms/ml, or substance P, 4 micrograms/ml, before and during renal pelvic perfusion with the prostaglandin synthesis inhibitor indomethacin, 50 micrograms/ml. Indomethacin reduced the peak ipsilateral afferent renal nerve activity responses to capsaicin and substance P by 83 +/- 15% and 81 +/- 8%, respectively, as well as the contralateral diuretic and natriuretic responses. We also examined the effects of renal pelvic administration of indomethacin on the responses to renal pelvic perfusion with bradykinin. Bradykinin, 20 micrograms/ml, increased peak ipsilateral afferent renal nerve activity by 197 +/- 47% and contralateral urine flow rate and urinary sodium excretion by 31 +/- 6 and 20 +/- 6%, respectively. Indomethacin reduced the ipsilateral afferent renal nerve activity response by 76 +/- 9% and abolished the contralateral diuretic and natriuretic responses to bradykinin. We conclude that renal sensory receptor activation by capsaicin, substance P, and bradykinin is dependent on intact renal prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Na(+)-K(+)-ATPase inhibition sensitizes renal mechanoreceptors activated by increases in renal pelvic pressure

1994 ◽  
Vol 267 (4) ◽  
pp. R1109-R1117 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith ◽  
A. L. Pence
Keyword(s):  
Membrane Potential ◽  
Resting Membrane Potential ◽  
Nerve Activity ◽  
Activation Threshold ◽  
Renal Nerve ◽  
Activity Response ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Atpase Inhibition ◽  
Pelvic Pressure

In anesthetized rats, the activation threshold of renal pelvic mechanoreceptors was determined by graded increases in renal pelvic pressure. Ipsilateral afferent renal nerve activity increased 9 +/- 4 (NS), 34 +/- 12, 47 +/- 8, 58 +/- 13, 68 +/- 14, and 91 +/- 17% (all P < 0.01) by the increase in renal pelvic pressure from 2.5 to 15 mmHg in 2.5-mmHg steps. Contralateral diuresis and natriuresis were elicited by renal pelvic pressures > 2.5 mmHg. Renal pelvic perfusion with 1.4 mM ouabain, an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), increased basal afferent renal nerve activity transiently, lowered the activation threshold of renal mechanoreceptors to < 2.5 mmHg, and enhanced the afferent renal nerve activity, responses to increasing renal pelvic pressures by 8 and 30 mmHg. The afferent renal nerve activity response to increased renal pelvic pressure was also enhanced by renal pelvic perfusion with 900 mM NaCl but was unaltered by NaCl concentrations ranging from 10 to 600 mM. These findings show that renal pelvic mechanoreceptors are activated by increases in renal pelvic pressure within the physiological range. Although renal Na(+)-K(+)-ATPase contributes to the maintenance of the resting membrane potential of renal pelvic mechanoreceptors, the renal pelvic mechanoreceptor discharge is not influenced by physiological renal pelvic Na+ concentrations.

Neuronal regulation of renal function: A model system for nervous system interactions

1992 ◽  
Vol 70 (5) ◽  
pp. 733-734 ◽  
Author(s):  
J. Michael Wyss
Keyword(s):  
Nervous System ◽  
Renal Function ◽  
Renal Disease ◽  
Easy Access ◽  
Renal Nerves ◽  
Clinical Consequence ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity

The kidney is the most highly innervated peripheral organ, and both the excretory and endocrine functions of the kidney are regulated by renal nerve activity. The kidney plays a dominant role in body fluid homeostasis, blood ionic concentration, and pH and thereby contributes importantly to systemic blood pressure control. Early studies suggested that the neural-renal interactions were responsible only for short-term adjustments in renal function, but more recent studies indicate that the renal nerves may be a major contributor to chronic renal defects leading to established hypertension and (or) renal disease. The neural-renal interaction is also of considerable interest as a model to elucidate the interplay between the nervous system and peripheral organs, since there is abundant anatomical and physiological information characterizing the renal nerves. The investigator has easy access to the renal nerves and the neural influence on renal function is directly quantifiable both in vivo and in vitro. In this symposium that was presented at the 1990 annual convention of the Society for Neuroscience in St. Louis, Missouri, three prominent researchers evaluate the most recent progress in understanding the interplay between the nervous system and the kidney and explore how the results of these studies relate to the broader questions concerning the nervous system's interactions.First, Luciano Barajas examines the detailed anatomy of the intrarenal distribution of the efferent and afferent renal nerves along the nephron and vasculature, and he evaluates the physiological role of each of the discrete components of the innervation. His basic science orientation combined with his deep appreciation of the clinical consequence of the failure of neural-renal regulation enhances his discussion of the anatomy. Ulla C. Kopp discusses the role of the renorenal reflex, which alters renal responses following stimulation of the contralateral kidney. She also considers her recent findings that efferent renal nerve activity can directly modify sensory feedback to the spinal cord from the kidney. Finally, J. Michael Wyss examines the functional consequences of neural control of the kidney in health and disease. Although the nervous system has often been considered as only an acute regulator of visceral function, current studies into hypertension and renal disease suggest that neural-renal dysfunction may be an important contributor to chronic diseases.Together, these presentations examine most of the recent advances in the area of neural-renal interactions and point out how these data form a basis for future research into neuronal interactions with all visceral organs. The relative simplicity of the neural-renal interaction makes this system an important model with which to elucidate all neural-peripheral and neural-neural interactions.

Lack of effect of chronic renal denervation on altered sodium reabsorption during increased ureteral pressure

1980 ◽  
Vol 58 (5) ◽  
pp. 477-483 ◽  
Author(s):  
D. R. Wilson ◽  
M. Cusimano ◽  
U. Honrath
Keyword(s):  
Isotonic Saline ◽  
Urine Osmolality ◽  
Tubular Reabsorption ◽  
Renal Nerves ◽  
Sodium Reabsorption ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Water Excretion ◽  
Renal Nerve Activity

The role of the renal nerves in the altered sodium reabsorption which occurs during increased ureteral pressure was studied using clearance techniques in anaesthetized rats undergoing diuresis induced by isotonic saline infusion. In rats with a sham denervated kidney, an ipsilateral increase in ureteral pressure to 20 cm H2O resulted in a marked and significant decrease in sodium and water excretion, increased fractional sodium reabsorption, and increased urine osmolality with no significant change in glomerular filtration rate. A similar significant ipsilateral increase in tubular reabsorption of sodium occurred in rats with chronically denervated kidneys during increased ureteral pressure. The changes in tubular reabsorption were rapidly reversible after return of ureteral pressure to normal. These experiments indicate that enhanced tubular reabsorption of sodium during an ipsilateral increase in ureteral pressure is not mediated by increased renal nerve activity. During the antinatriuresis of increased ureteral pressure there was a decrease in the fractional reabsorption of sodium from the opposite normal kidney. The role of the renal nerves in this compensatory change in function in the opposite kidney was studied in two further groups of animals. The renal response to a contralateral increase in ureteral pressure was similar in denervated and sham-denervated kidneys. The results indicate that altered renal nerve activity, through ipsilateral or contralateral renorenal reflexes, is not responsible for the changes in tubular reabsorption of sodium which occur during increased ureteral pressure induced by partial ureteral obstruction.

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