Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes

Br J Pharmacol. 2015 Aug;172(16):3980-4001. doi: 10.1111/bph.13205. Epub 2015 Jul 8.

Abstract

Vascular dysfunction plays a pivotal role in the development of systemic complications associated with arterial hypertension and diabetes. The endothelium, or more specifically, various factors derived from endothelial cells tightly regulate vascular function, including vascular tone. In physiological conditions, there is a balance between endothelium-derived factors, that is, relaxing factors (endothelium-derived relaxing factors; EDRFs) and contracting factors (endothelium-derived contracting factors; EDCFs), which mediate vascular homeostasis. However, in disease states, such as diabetes and arterial hypertension, there is an imbalance between EDRF and EDCF, with a reduction of EDRF signalling and an increase of EDCF signalling. Among EDCFs, COX-derived vasoconstrictor prostanoids play an important role in the development of vascular dysfunction associated with hypertension and diabetes. Moreover, uridine adenosine tetraphosphate (Up4 A), identified as an EDCF in 2005, also modulates vascular function. However, the role of Up4 A in hypertension- and diabetes-associated vascular dysfunction is unclear. In the present review, we focused on experimental and clinical evidence that implicate these two EDCFs (vasoconstrictor prostanoids and Up4 A) in vascular dysfunction associated with hypertension and diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology
  • Dinucleoside Phosphates / metabolism*
  • Dinucleoside Phosphates / physiology
  • Endothelins / metabolism
  • Endothelins / physiology
  • Gonadal Steroid Hormones / metabolism
  • Humans
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Myocytes, Smooth Muscle / metabolism
  • Prostaglandin-Endoperoxide Synthases / physiology
  • Prostaglandins / metabolism*
  • Prostaglandins / physiology
  • Vasoconstriction / physiology

Substances

  • Dinucleoside Phosphates
  • Endothelins
  • Gonadal Steroid Hormones
  • Prostaglandins
  • uridine adenosine tetraphosphate
  • Prostaglandin-Endoperoxide Synthases