Endothelin-1 and pancreatic islet vasculature : studies in vivo and on isolated, vascularly perfused pancreatic islets

• Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate whether exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo, we found that ET-1 (5 nmol/kg) consistently and markedly decreased total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin A (ET(A)) receptor (BQ-123) nor endothelin-B (ET(B)) receptor (BQ-788) antagonists, alone or in combination, could prevent this reduction in blood flow. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation, we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ET(A) receptors.

Nyckelord

Adrenal Glands/blood supply

Animals

Arterioles/physiology

Blood Glucose/metabolism

Blood Pressure/drug effects

Colon/blood supply

Drug Synergism

Duodenum/blood supply

Endothelin-1/*pharmacology

Insulin/blood

Islets of Langerhans/*blood supply

Male

Mice

Mice; Inbred C57BL

Oligopeptides/pharmacology

Pancreas/blood supply

Peptides; Cyclic/pharmacology

Piperidines/pharmacology

Rats

Rats; Sprague-Dawley

Receptor; Endothelin A/antagonists & inhibitors

Receptor; Endothelin B/antagonists & inhibitors

Regional Blood Flow/drug effects

Vasoconstriction

MEDICINE

MEDICIN

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