Inhibition of nitric oxide synthesis accentuates blood pressure elevation in hyperinsulinemic rats

Te Chao Fang, Chin Chen Wu, Wann Chu Huang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objectives: To examine the role of endogenous nitric oxide (NO) in the pathogenesis of hypertension and insulin resistance in chronic hyperinsulinemia rats. Methods: Sustained hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per min) via subcutaneous osmotic minipump for 6 weeks. NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg per day) was given orally after 4 weeks of vehicle or insulin infusion. The systolic blood pressure (SBP) was measured under conscious state by an electrosphygmomanometer before and after drug treatments. Results: Insulin infusion alone significantly increased SBP from 134 ± 3 to 156 ± 2 mmHg by week 4 and further to 158 ± 3 mmHg by week 6 of insulin infusion. The insulin-infused rats had markedly decreased insulin sensitivity, as reflected by an elevated steady-state plasma glucose level estimated by the insulin suppression test. There were no significant differences in plasma glucose and triglyceride levels between rats with and without insulin infusion. When hypertension had been established in rats receiving insulin infusion for 4 weeks, superimposed L-NAME on insulin infusion for additional 2 weeks further increased SBP by 18 ± 2 mmHg (from 157 ± 2 to 175 ± 2 mmHg). Plasma levels of NO metabolites (NOx) significantly decreased from 13.7 ± 1.1 μmol/I during the control period to 6.1 ± 0.6 μmol/I after 4 weeks of insulin infusion and further reduced to 4.1 ± 0.5 μmol/I after combined infusion of L-NAME and insulin. L-NAME treatment alone for 2 weeks in control rats significantly increased SBP by 33 ± 2 mmHg (from 133 ± 2 to 166 ± 2 mmHg) and plasma insulin levels, as a consequence of insulin resistance. Despite marked increases in blood pressure due to infusion of insulin alone or in combination with L-NAME, the sodium balance, urinary sodium and water excretions, water intake and body weight gain of insulin/L-NAME-treated rats were not significantly different from rats without insulin infusion. Conclusions: Sustained hyperinsulinemia causes partial impairment of NO production that may contribute to the development of insulin resistance and hypertension. Additional inhibition of NO synthesis by L-NAME accentuates the blood pressure elevation and insulin resistance in hyperinsulinemia rats. Furthermore, a rightward shift of the renal arterial pressure-natriuretic function relationship occurred in this hypertensive model.

Original languageEnglish
Pages (from-to)1255-1262
Number of pages8
JournalJournal of Hypertension
Volume19
Issue number7
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Nitric Oxide
Insulin
Blood Pressure
NG-Nitroarginine Methyl Ester
Insulin Resistance
Hyperinsulinism
Hypertension
Sodium
Glucose
Nitric Oxide Synthase
Drinking
Weight Gain
Arterial Pressure
Triglycerides
Body Weight
Kidney

Keywords

  • Hyperinsulinemia
  • Hypertension
  • Insulin resistance
  • N-nitro-L-arginine methyl ester
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Inhibition of nitric oxide synthesis accentuates blood pressure elevation in hyperinsulinemic rats. / Fang, Te Chao; Wu, Chin Chen; Huang, Wann Chu.

In: Journal of Hypertension, Vol. 19, No. 7, 2001, p. 1255-1262.

Research output: Contribution to journalArticle

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abstract = "Objectives: To examine the role of endogenous nitric oxide (NO) in the pathogenesis of hypertension and insulin resistance in chronic hyperinsulinemia rats. Methods: Sustained hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per min) via subcutaneous osmotic minipump for 6 weeks. NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg per day) was given orally after 4 weeks of vehicle or insulin infusion. The systolic blood pressure (SBP) was measured under conscious state by an electrosphygmomanometer before and after drug treatments. Results: Insulin infusion alone significantly increased SBP from 134 ± 3 to 156 ± 2 mmHg by week 4 and further to 158 ± 3 mmHg by week 6 of insulin infusion. The insulin-infused rats had markedly decreased insulin sensitivity, as reflected by an elevated steady-state plasma glucose level estimated by the insulin suppression test. There were no significant differences in plasma glucose and triglyceride levels between rats with and without insulin infusion. When hypertension had been established in rats receiving insulin infusion for 4 weeks, superimposed L-NAME on insulin infusion for additional 2 weeks further increased SBP by 18 ± 2 mmHg (from 157 ± 2 to 175 ± 2 mmHg). Plasma levels of NO metabolites (NOx) significantly decreased from 13.7 ± 1.1 μmol/I during the control period to 6.1 ± 0.6 μmol/I after 4 weeks of insulin infusion and further reduced to 4.1 ± 0.5 μmol/I after combined infusion of L-NAME and insulin. L-NAME treatment alone for 2 weeks in control rats significantly increased SBP by 33 ± 2 mmHg (from 133 ± 2 to 166 ± 2 mmHg) and plasma insulin levels, as a consequence of insulin resistance. Despite marked increases in blood pressure due to infusion of insulin alone or in combination with L-NAME, the sodium balance, urinary sodium and water excretions, water intake and body weight gain of insulin/L-NAME-treated rats were not significantly different from rats without insulin infusion. Conclusions: Sustained hyperinsulinemia causes partial impairment of NO production that may contribute to the development of insulin resistance and hypertension. Additional inhibition of NO synthesis by L-NAME accentuates the blood pressure elevation and insulin resistance in hyperinsulinemia rats. Furthermore, a rightward shift of the renal arterial pressure-natriuretic function relationship occurred in this hypertensive model.",
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T1 - Inhibition of nitric oxide synthesis accentuates blood pressure elevation in hyperinsulinemic rats

AU - Fang, Te Chao

AU - Wu, Chin Chen

AU - Huang, Wann Chu

PY - 2001

Y1 - 2001

N2 - Objectives: To examine the role of endogenous nitric oxide (NO) in the pathogenesis of hypertension and insulin resistance in chronic hyperinsulinemia rats. Methods: Sustained hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per min) via subcutaneous osmotic minipump for 6 weeks. NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg per day) was given orally after 4 weeks of vehicle or insulin infusion. The systolic blood pressure (SBP) was measured under conscious state by an electrosphygmomanometer before and after drug treatments. Results: Insulin infusion alone significantly increased SBP from 134 ± 3 to 156 ± 2 mmHg by week 4 and further to 158 ± 3 mmHg by week 6 of insulin infusion. The insulin-infused rats had markedly decreased insulin sensitivity, as reflected by an elevated steady-state plasma glucose level estimated by the insulin suppression test. There were no significant differences in plasma glucose and triglyceride levels between rats with and without insulin infusion. When hypertension had been established in rats receiving insulin infusion for 4 weeks, superimposed L-NAME on insulin infusion for additional 2 weeks further increased SBP by 18 ± 2 mmHg (from 157 ± 2 to 175 ± 2 mmHg). Plasma levels of NO metabolites (NOx) significantly decreased from 13.7 ± 1.1 μmol/I during the control period to 6.1 ± 0.6 μmol/I after 4 weeks of insulin infusion and further reduced to 4.1 ± 0.5 μmol/I after combined infusion of L-NAME and insulin. L-NAME treatment alone for 2 weeks in control rats significantly increased SBP by 33 ± 2 mmHg (from 133 ± 2 to 166 ± 2 mmHg) and plasma insulin levels, as a consequence of insulin resistance. Despite marked increases in blood pressure due to infusion of insulin alone or in combination with L-NAME, the sodium balance, urinary sodium and water excretions, water intake and body weight gain of insulin/L-NAME-treated rats were not significantly different from rats without insulin infusion. Conclusions: Sustained hyperinsulinemia causes partial impairment of NO production that may contribute to the development of insulin resistance and hypertension. Additional inhibition of NO synthesis by L-NAME accentuates the blood pressure elevation and insulin resistance in hyperinsulinemia rats. Furthermore, a rightward shift of the renal arterial pressure-natriuretic function relationship occurred in this hypertensive model.

AB - Objectives: To examine the role of endogenous nitric oxide (NO) in the pathogenesis of hypertension and insulin resistance in chronic hyperinsulinemia rats. Methods: Sustained hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per min) via subcutaneous osmotic minipump for 6 weeks. NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg per day) was given orally after 4 weeks of vehicle or insulin infusion. The systolic blood pressure (SBP) was measured under conscious state by an electrosphygmomanometer before and after drug treatments. Results: Insulin infusion alone significantly increased SBP from 134 ± 3 to 156 ± 2 mmHg by week 4 and further to 158 ± 3 mmHg by week 6 of insulin infusion. The insulin-infused rats had markedly decreased insulin sensitivity, as reflected by an elevated steady-state plasma glucose level estimated by the insulin suppression test. There were no significant differences in plasma glucose and triglyceride levels between rats with and without insulin infusion. When hypertension had been established in rats receiving insulin infusion for 4 weeks, superimposed L-NAME on insulin infusion for additional 2 weeks further increased SBP by 18 ± 2 mmHg (from 157 ± 2 to 175 ± 2 mmHg). Plasma levels of NO metabolites (NOx) significantly decreased from 13.7 ± 1.1 μmol/I during the control period to 6.1 ± 0.6 μmol/I after 4 weeks of insulin infusion and further reduced to 4.1 ± 0.5 μmol/I after combined infusion of L-NAME and insulin. L-NAME treatment alone for 2 weeks in control rats significantly increased SBP by 33 ± 2 mmHg (from 133 ± 2 to 166 ± 2 mmHg) and plasma insulin levels, as a consequence of insulin resistance. Despite marked increases in blood pressure due to infusion of insulin alone or in combination with L-NAME, the sodium balance, urinary sodium and water excretions, water intake and body weight gain of insulin/L-NAME-treated rats were not significantly different from rats without insulin infusion. Conclusions: Sustained hyperinsulinemia causes partial impairment of NO production that may contribute to the development of insulin resistance and hypertension. Additional inhibition of NO synthesis by L-NAME accentuates the blood pressure elevation and insulin resistance in hyperinsulinemia rats. Furthermore, a rightward shift of the renal arterial pressure-natriuretic function relationship occurred in this hypertensive model.

KW - Hyperinsulinemia

KW - Hypertension

KW - Insulin resistance

KW - N-nitro-L-arginine methyl ester

KW - Nitric oxide

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