Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats

Chiang Ting Chien, Hsiung Fei Chien, Ya Jong Cheng, Chau Fong Chen, Su Ming Hsu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. Methods. Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. Results. In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. Conclusion. Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalKidney International
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 1 2000
Externally publishedYes

Fingerprint

Mechanoreceptors
Streptozocin
Diuretics
Kidney
Reflex
Insulin
Histamine
Urine
Pressure
Complement 3d Receptors
Therapeutics
Kidney Pelvis
Aptitude
Histamine Antagonists
Sensory Receptor Cells
Hyperglycemia
Renal Insufficiency
Blood Vessels
Tail
Veins

Keywords

  • Diabetes
  • Mechanoreceptor
  • Renal chemoreceptor
  • Renorenal reflex
  • Volume expansion

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats. / Chien, Chiang Ting; Chien, Hsiung Fei; Cheng, Ya Jong; Chen, Chau Fong; Hsu, Su Ming.

In: Kidney International, Vol. 57, No. 1, 01.01.2000, p. 203-214.

Research output: Contribution to journalArticle

Chien, Chiang Ting ; Chien, Hsiung Fei ; Cheng, Ya Jong ; Chen, Chau Fong ; Hsu, Su Ming. / Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats. In: Kidney International. 2000 ; Vol. 57, No. 1. pp. 203-214.
@article{a24f2f231be848eea81c07ea0e96b3fe,
title = "Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats",
abstract = "Background. Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. Methods. Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. Results. In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. Conclusion. Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.",
keywords = "Diabetes, Mechanoreceptor, Renal chemoreceptor, Renorenal reflex, Volume expansion",
author = "Chien, {Chiang Ting} and Chien, {Hsiung Fei} and Cheng, {Ya Jong} and Chen, {Chau Fong} and Hsu, {Su Ming}",
year = "2000",
month = "1",
day = "1",
doi = "10.1046/j.1523-1755.2000.00826.x",
language = "English",
volume = "57",
pages = "203--214",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats

AU - Chien, Chiang Ting

AU - Chien, Hsiung Fei

AU - Cheng, Ya Jong

AU - Chen, Chau Fong

AU - Hsu, Su Ming

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background. Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. Methods. Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. Results. In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. Conclusion. Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.

AB - Background. Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. Methods. Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. Results. In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. Conclusion. Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.

KW - Diabetes

KW - Mechanoreceptor

KW - Renal chemoreceptor

KW - Renorenal reflex

KW - Volume expansion

UR - http://www.scopus.com/inward/record.url?scp=0033995717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033995717&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2000.00826.x

DO - 10.1046/j.1523-1755.2000.00826.x

M3 - Article

C2 - 10620201

AN - SCOPUS:0033995717

VL - 57

SP - 203

EP - 214

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -