Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Giulia Calenda, Yuehong Tong, Nirmala D. Kanika, Moses T. Tar, Sylvia O. Suadicani, Xinhua Zhang, Arnold Melman, Catherine Rougeot, Kelvin Davies

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011

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glutaminyl-arginyl-phenylalanyl-seryl-arginine
Type 1 Diabetes Mellitus
Peptides
Erectile Dysfunction
Blood Vessels
C-Type Natriuretic Peptide
Men's Health
Gene Expression
Aptitude
Bradykinin
Vascular Smooth Muscle
Biochemistry
Smooth Muscle Myocytes
Coronary Disease
Smooth Muscle
Plasmids
Myocardial Infarction
Blood Pressure
Hypertension
Calcium

Keywords

  • Erectile dysfunction
  • Hypertension
  • Sialorphin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides. / Calenda, Giulia; Tong, Yuehong; Kanika, Nirmala D.; Tar, Moses T.; Suadicani, Sylvia O.; Zhang, Xinhua; Melman, Arnold; Rougeot, Catherine; Davies, Kelvin.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 4, 10.2011.

Research output: Contribution to journalArticle

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