Renal responsiveness to atrial natriuretic peptide in the noninsulin-dependent diabetic rat

B. K. Warren, Mahmood S Mozaffari, C. B. Patel

Research output: Contribution to journalArticle

Abstract

Total body sodium is elevated in noninsulin-dependent diabetes (NIDD) and is implicated in the greater prevalence of systemic hypertension in this population. Given the pivotal role of atrial natriuretic peptide (ANP) in sodium homeostasis, we tested the hypothesis that reduced renal responsiveness to ANP contributes to the sodium retention in NIDD. Two-day old male Sprague-Dawley rats were injected with either streptozotocin (90 mg/kg BW, i.p.; NIDD, n=9) or vehicle (citrate buffer, pH 4.3; control, n=7). At three months of age, diabetes was confirmed by the administration of a glucose tolerance test (2g/Kg, i.p.) which resulted in significantly, greater elevations in blood glucose concentration in the NIDD than control rats. In preparation for renal functional studies, each rat was implanted with femoral vessel cannulae and a bladder catheter, under ether anesthesia. Two days after the surgery, renal excretory responses to a 30 minute infusion of ANP (0.5 μg/min/kg, i.v.) were determined in the conscious rat. This was followed by two, consecutive, 30 minute, recovery periods. Baseline sodium excretion was similar between the groups, while fluid excretion was slightly, albeit significantly, lower in the NIDD rats. The infusion of ANP increased renal fluid and sodium excretion in both groups; however, the natriuretic response was significantly lower in the NIDD than control rats. Thirty minutes after cessation of ANP infusion, renal excretions of fluid and sodium returned towards baseline values in the control rats. In contrast, the NIDD rats maintained elevated fluid and sodium excretions during the recovery periods. Baseline glomerular filtration rate, measured as the rate of 3H-inulin clearance, was similar between the groups and not significantly affected by ANP infusion. Therefore, the natriuretic and diuretic effects of ANP were mediated by reduced tubular reabsorption of fluid and sodium, as indexed by increased fractional excretion of fluid and sodium. In conclusion, the diabetic rat demonstrated a reduced natriuretic response to the infusion of ANP but sustained elevations in fluid and sodium excretions after cessation of ANP infusion.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Jan 1 1999

Fingerprint

Atrial Natriuretic Factor
Rats
Medical problems
Sodium
Kidney
Rat control
Fluids
Natriuretic Agents
Recovery
Inulin
Catheters
Glucose Tolerance Test
Streptozocin
Thigh
Glomerular Filtration Rate
Ambulatory Surgical Procedures
Diuretics
Citric Acid
Ether
Surgery

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Renal responsiveness to atrial natriuretic peptide in the noninsulin-dependent diabetic rat. / Warren, B. K.; Mozaffari, Mahmood S; Patel, C. B.

In: Journal of Investigative Medicine, Vol. 47, No. 2, 01.01.1999.

Research output: Contribution to journalArticle

@article{5ad8343f8a9b4f679f8646d8e380d636,
title = "Renal responsiveness to atrial natriuretic peptide in the noninsulin-dependent diabetic rat",
abstract = "Total body sodium is elevated in noninsulin-dependent diabetes (NIDD) and is implicated in the greater prevalence of systemic hypertension in this population. Given the pivotal role of atrial natriuretic peptide (ANP) in sodium homeostasis, we tested the hypothesis that reduced renal responsiveness to ANP contributes to the sodium retention in NIDD. Two-day old male Sprague-Dawley rats were injected with either streptozotocin (90 mg/kg BW, i.p.; NIDD, n=9) or vehicle (citrate buffer, pH 4.3; control, n=7). At three months of age, diabetes was confirmed by the administration of a glucose tolerance test (2g/Kg, i.p.) which resulted in significantly, greater elevations in blood glucose concentration in the NIDD than control rats. In preparation for renal functional studies, each rat was implanted with femoral vessel cannulae and a bladder catheter, under ether anesthesia. Two days after the surgery, renal excretory responses to a 30 minute infusion of ANP (0.5 μg/min/kg, i.v.) were determined in the conscious rat. This was followed by two, consecutive, 30 minute, recovery periods. Baseline sodium excretion was similar between the groups, while fluid excretion was slightly, albeit significantly, lower in the NIDD rats. The infusion of ANP increased renal fluid and sodium excretion in both groups; however, the natriuretic response was significantly lower in the NIDD than control rats. Thirty minutes after cessation of ANP infusion, renal excretions of fluid and sodium returned towards baseline values in the control rats. In contrast, the NIDD rats maintained elevated fluid and sodium excretions during the recovery periods. Baseline glomerular filtration rate, measured as the rate of 3H-inulin clearance, was similar between the groups and not significantly affected by ANP infusion. Therefore, the natriuretic and diuretic effects of ANP were mediated by reduced tubular reabsorption of fluid and sodium, as indexed by increased fractional excretion of fluid and sodium. In conclusion, the diabetic rat demonstrated a reduced natriuretic response to the infusion of ANP but sustained elevations in fluid and sodium excretions after cessation of ANP infusion.",
author = "Warren, {B. K.} and Mozaffari, {Mahmood S} and Patel, {C. B.}",
year = "1999",
month = "1",
day = "1",
language = "English (US)",
volume = "47",
journal = "Journal of Investigative Medicine",
issn = "1081-5589",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Renal responsiveness to atrial natriuretic peptide in the noninsulin-dependent diabetic rat

AU - Warren, B. K.

AU - Mozaffari, Mahmood S

AU - Patel, C. B.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Total body sodium is elevated in noninsulin-dependent diabetes (NIDD) and is implicated in the greater prevalence of systemic hypertension in this population. Given the pivotal role of atrial natriuretic peptide (ANP) in sodium homeostasis, we tested the hypothesis that reduced renal responsiveness to ANP contributes to the sodium retention in NIDD. Two-day old male Sprague-Dawley rats were injected with either streptozotocin (90 mg/kg BW, i.p.; NIDD, n=9) or vehicle (citrate buffer, pH 4.3; control, n=7). At three months of age, diabetes was confirmed by the administration of a glucose tolerance test (2g/Kg, i.p.) which resulted in significantly, greater elevations in blood glucose concentration in the NIDD than control rats. In preparation for renal functional studies, each rat was implanted with femoral vessel cannulae and a bladder catheter, under ether anesthesia. Two days after the surgery, renal excretory responses to a 30 minute infusion of ANP (0.5 μg/min/kg, i.v.) were determined in the conscious rat. This was followed by two, consecutive, 30 minute, recovery periods. Baseline sodium excretion was similar between the groups, while fluid excretion was slightly, albeit significantly, lower in the NIDD rats. The infusion of ANP increased renal fluid and sodium excretion in both groups; however, the natriuretic response was significantly lower in the NIDD than control rats. Thirty minutes after cessation of ANP infusion, renal excretions of fluid and sodium returned towards baseline values in the control rats. In contrast, the NIDD rats maintained elevated fluid and sodium excretions during the recovery periods. Baseline glomerular filtration rate, measured as the rate of 3H-inulin clearance, was similar between the groups and not significantly affected by ANP infusion. Therefore, the natriuretic and diuretic effects of ANP were mediated by reduced tubular reabsorption of fluid and sodium, as indexed by increased fractional excretion of fluid and sodium. In conclusion, the diabetic rat demonstrated a reduced natriuretic response to the infusion of ANP but sustained elevations in fluid and sodium excretions after cessation of ANP infusion.

AB - Total body sodium is elevated in noninsulin-dependent diabetes (NIDD) and is implicated in the greater prevalence of systemic hypertension in this population. Given the pivotal role of atrial natriuretic peptide (ANP) in sodium homeostasis, we tested the hypothesis that reduced renal responsiveness to ANP contributes to the sodium retention in NIDD. Two-day old male Sprague-Dawley rats were injected with either streptozotocin (90 mg/kg BW, i.p.; NIDD, n=9) or vehicle (citrate buffer, pH 4.3; control, n=7). At three months of age, diabetes was confirmed by the administration of a glucose tolerance test (2g/Kg, i.p.) which resulted in significantly, greater elevations in blood glucose concentration in the NIDD than control rats. In preparation for renal functional studies, each rat was implanted with femoral vessel cannulae and a bladder catheter, under ether anesthesia. Two days after the surgery, renal excretory responses to a 30 minute infusion of ANP (0.5 μg/min/kg, i.v.) were determined in the conscious rat. This was followed by two, consecutive, 30 minute, recovery periods. Baseline sodium excretion was similar between the groups, while fluid excretion was slightly, albeit significantly, lower in the NIDD rats. The infusion of ANP increased renal fluid and sodium excretion in both groups; however, the natriuretic response was significantly lower in the NIDD than control rats. Thirty minutes after cessation of ANP infusion, renal excretions of fluid and sodium returned towards baseline values in the control rats. In contrast, the NIDD rats maintained elevated fluid and sodium excretions during the recovery periods. Baseline glomerular filtration rate, measured as the rate of 3H-inulin clearance, was similar between the groups and not significantly affected by ANP infusion. Therefore, the natriuretic and diuretic effects of ANP were mediated by reduced tubular reabsorption of fluid and sodium, as indexed by increased fractional excretion of fluid and sodium. In conclusion, the diabetic rat demonstrated a reduced natriuretic response to the infusion of ANP but sustained elevations in fluid and sodium excretions after cessation of ANP infusion.

UR - http://www.scopus.com/inward/record.url?scp=33750105002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750105002&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750105002

VL - 47

JO - Journal of Investigative Medicine

JF - Journal of Investigative Medicine

SN - 1081-5589

IS - 2

ER -