Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats

P. Murray, B. Pitt, R Clinton Webb

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

This study investigated the protective effect of the angiotensin converting enzyme inhibitor, ramipril, on endothelium-dependent responses in arteries from control (CON) and streptozotocin-induced (STZ) diabetic rats. Three hypotheses were tested: 1) there is an endothelium-dependent component to the increased alpha-adrenergic responsiveness characteristic of diabetes; 2) endothelium-dependent, acetylcholine-induced relaxation is attenuated in aorta from diabetic rats; and 3) ramipril (3 mg/kg daily in the food, 12-15 weeks) will prevent functional vascular changes in diabetic rats. Vascular function was assessed in aortic rings using standard muscle bath procedures for measurement of isometric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD2 values (-log ED50): CON=6.22±0.12, STZ=7.54±0.11), and removal of the endothelium (-Endo) increased phenylephrine sensitivity (CON-Endo=7.40±0.11, STZ-Endo=8.32±0.18). The magnitude of the shift in responsiveness following endothelium removal was greatest in control rats. Ramipril treatment (Ram) partially normalized phenylephrine responsiveness in intact (STZ + Ram=6.55±0.11) and denuded (STZ-Endo + Ram=7.75±0.10) vessels. Vasodilatation to acetylcholine and nitroglycerin was not altered in diabetic rats nor was it affected by ramipril treatment. Diabetes increases contractile sensitivity to phenylephrine but not to vasodilators and chronic ramipril treatment prevents this increase in contractile sensitivity. Ramipril treatment did not alter the hyperglycaemic condition induced by streptozotocin. The changes in phenylephrine sensitivity appear to involve an endothelial and a smooth muscle component.

Original languageEnglish (US)
Pages (from-to)664-670
Number of pages7
JournalDiabetologia
Volume37
Issue number7
DOIs
StatePublished - Jul 1 1994

Fingerprint

Ramipril
Phenylephrine
Streptozocin
Aorta
Hypersensitivity
Endothelium
Acetylcholine
Blood Vessels
Nitroglycerin
Therapeutics
Vasodilator Agents
Baths
Angiotensin-Converting Enzyme Inhibitors
Vasodilation
Adrenergic Agents
Smooth Muscle
Arteries
Food
Muscles

Keywords

  • Endothelium
  • acetylcholine
  • angiotensin
  • converting enzyme inhibitor
  • vascular smooth muscle

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats. / Murray, P.; Pitt, B.; Webb, R Clinton.

In: Diabetologia, Vol. 37, No. 7, 01.07.1994, p. 664-670.

Research output: Contribution to journalArticle

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