NaCl-induced hypertensive rat model of non-insulin-dependent diabetes: Role of sympathetic modulation

Mahmood S Mozaffari, Champa Patel, Brett K. Warren, Stephen W. Schaffer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Systemic hypertension is common in individuals with non-insulin-dependent diabetes (NIDD) and, in this population, markedly increases the risk for cardiovascular complications. The aims of this study were to develop a rat model of combined NaCl-induced hypertension and NIDD, and to determine the contribution of the sympathetic nervous system to the development of the manifest hypertension. Two-day old male Wistar-Kyoto rats were injected with either streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one group maintained on normal (0.72 %) NaCl diet whereas the other was placed on a high (8%)-NaCl diet. At 6 months of age, diabetes was confirmed by glucose tolerance testing. Hemodynamic parameters were measured in the freely moving animal (ia) before and after the administration of prazosin (peripheral α1-adrenergic antagonist, iv) or clonidine (central α2-adrenergic agonist). The NIDD rat displayed a higher (P < .05) blood glucose concentration than the nondiabetic control rat during the glucose tolerance test. Elevated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administration of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clonidine caused a significant reduction in MAP of the hypertensive control rat but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in response to clonidine administration. The data suggest that the combination of uninephrectomy and dietary NaCl excess confers hypertension on the NIDD rat. Moreover, enhancement of the sympathetic pathway plays an important role in the regulation of arterial pressure in the hypertensive NIDD rat.

Original languageEnglish (US)
Pages (from-to)540-546
Number of pages7
JournalAmerican Journal of Hypertension
Volume13
Issue number5 II SUPPL.
StatePublished - Dec 1 2000

Fingerprint

Arterial Pressure
Clonidine
Hypertension
Prazosin
Diet
Adrenergic Agonists
Adrenergic Antagonists
Inbred WKY Rats
Sympathetic Nervous System
Glucose Tolerance Test
Streptozocin
Nephrectomy
Citric Acid
Blood Glucose
Buffers
Hemodynamics
Glucose
Population

Keywords

  • Clonidine
  • Prazosin
  • Rat
  • Salt-induced hypertension
  • Type II diabetes

ASJC Scopus subject areas

  • Internal Medicine

Cite this

NaCl-induced hypertensive rat model of non-insulin-dependent diabetes : Role of sympathetic modulation. / Mozaffari, Mahmood S; Patel, Champa; Warren, Brett K.; Schaffer, Stephen W.

In: American Journal of Hypertension, Vol. 13, No. 5 II SUPPL., 01.12.2000, p. 540-546.

Research output: Contribution to journalArticle

Mozaffari, Mahmood S ; Patel, Champa ; Warren, Brett K. ; Schaffer, Stephen W. / NaCl-induced hypertensive rat model of non-insulin-dependent diabetes : Role of sympathetic modulation. In: American Journal of Hypertension. 2000 ; Vol. 13, No. 5 II SUPPL. pp. 540-546.
@article{f432de8bfde6492985b4b98e13dacdb3,
title = "NaCl-induced hypertensive rat model of non-insulin-dependent diabetes: Role of sympathetic modulation",
abstract = "Systemic hypertension is common in individuals with non-insulin-dependent diabetes (NIDD) and, in this population, markedly increases the risk for cardiovascular complications. The aims of this study were to develop a rat model of combined NaCl-induced hypertension and NIDD, and to determine the contribution of the sympathetic nervous system to the development of the manifest hypertension. Two-day old male Wistar-Kyoto rats were injected with either streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one group maintained on normal (0.72 {\%}) NaCl diet whereas the other was placed on a high (8{\%})-NaCl diet. At 6 months of age, diabetes was confirmed by glucose tolerance testing. Hemodynamic parameters were measured in the freely moving animal (ia) before and after the administration of prazosin (peripheral α1-adrenergic antagonist, iv) or clonidine (central α2-adrenergic agonist). The NIDD rat displayed a higher (P < .05) blood glucose concentration than the nondiabetic control rat during the glucose tolerance test. Elevated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administration of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clonidine caused a significant reduction in MAP of the hypertensive control rat but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in response to clonidine administration. The data suggest that the combination of uninephrectomy and dietary NaCl excess confers hypertension on the NIDD rat. Moreover, enhancement of the sympathetic pathway plays an important role in the regulation of arterial pressure in the hypertensive NIDD rat.",
keywords = "Clonidine, Prazosin, Rat, Salt-induced hypertension, Type II diabetes",
author = "Mozaffari, {Mahmood S} and Champa Patel and Warren, {Brett K.} and Schaffer, {Stephen W.}",
year = "2000",
month = "12",
day = "1",
language = "English (US)",
volume = "13",
pages = "540--546",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "5 II SUPPL.",

}

TY - JOUR

T1 - NaCl-induced hypertensive rat model of non-insulin-dependent diabetes

T2 - Role of sympathetic modulation

AU - Mozaffari, Mahmood S

AU - Patel, Champa

AU - Warren, Brett K.

AU - Schaffer, Stephen W.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Systemic hypertension is common in individuals with non-insulin-dependent diabetes (NIDD) and, in this population, markedly increases the risk for cardiovascular complications. The aims of this study were to develop a rat model of combined NaCl-induced hypertension and NIDD, and to determine the contribution of the sympathetic nervous system to the development of the manifest hypertension. Two-day old male Wistar-Kyoto rats were injected with either streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one group maintained on normal (0.72 %) NaCl diet whereas the other was placed on a high (8%)-NaCl diet. At 6 months of age, diabetes was confirmed by glucose tolerance testing. Hemodynamic parameters were measured in the freely moving animal (ia) before and after the administration of prazosin (peripheral α1-adrenergic antagonist, iv) or clonidine (central α2-adrenergic agonist). The NIDD rat displayed a higher (P < .05) blood glucose concentration than the nondiabetic control rat during the glucose tolerance test. Elevated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administration of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clonidine caused a significant reduction in MAP of the hypertensive control rat but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in response to clonidine administration. The data suggest that the combination of uninephrectomy and dietary NaCl excess confers hypertension on the NIDD rat. Moreover, enhancement of the sympathetic pathway plays an important role in the regulation of arterial pressure in the hypertensive NIDD rat.

AB - Systemic hypertension is common in individuals with non-insulin-dependent diabetes (NIDD) and, in this population, markedly increases the risk for cardiovascular complications. The aims of this study were to develop a rat model of combined NaCl-induced hypertension and NIDD, and to determine the contribution of the sympathetic nervous system to the development of the manifest hypertension. Two-day old male Wistar-Kyoto rats were injected with either streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one group maintained on normal (0.72 %) NaCl diet whereas the other was placed on a high (8%)-NaCl diet. At 6 months of age, diabetes was confirmed by glucose tolerance testing. Hemodynamic parameters were measured in the freely moving animal (ia) before and after the administration of prazosin (peripheral α1-adrenergic antagonist, iv) or clonidine (central α2-adrenergic agonist). The NIDD rat displayed a higher (P < .05) blood glucose concentration than the nondiabetic control rat during the glucose tolerance test. Elevated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administration of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clonidine caused a significant reduction in MAP of the hypertensive control rat but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in response to clonidine administration. The data suggest that the combination of uninephrectomy and dietary NaCl excess confers hypertension on the NIDD rat. Moreover, enhancement of the sympathetic pathway plays an important role in the regulation of arterial pressure in the hypertensive NIDD rat.

KW - Clonidine

KW - Prazosin

KW - Rat

KW - Salt-induced hypertension

KW - Type II diabetes

UR - http://www.scopus.com/inward/record.url?scp=0034077260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034077260&partnerID=8YFLogxK

M3 - Article

C2 - 10826407

AN - SCOPUS:0034077260

VL - 13

SP - 540

EP - 546

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 5 II SUPPL.

ER -