PS 01-17] HYPERTENSION PROMOTES ISLET MORPHOLOGICAL CHANGES WITH VASCULAR INJURY ON PRE-DIABETIC STATUS IN SHR-SP RATS

Abstract

Objective: Type 2 diabetes causes not only insulin resistance but also failure of insulin producing β cells resulting in insufficient insulin secretion. Hypertensive patients have a higher incidence of new-onset diabetic mellitus than normotensive subjects, and we hypothesized that hypertension induces morphological changes in islets via vascular injury. To test our hypothesis, we administrated hydralazine or irbesartan to spontaneously hypertensive stroke-prone (SHRsp)/Izm male rats. Design and Method: SHRsp rats were randomly divided into three groups (SHRsp, SHRsp+Hyd, and SHRsp+Irb). The SHRsp+Hyd group was administrated hydralazine (5.0 mg body–1 d–1) by the gavage method, and the SHRsp+Irb group was similarly administrated irbesartan (50 m g body–1 d–1) from the age of 6 weeks until 20 weeks. Systolic blood pressure (SBP) and heart rate were measured weekly by the tail-cuff method. Blood samples were obtained via cardiac puncture to measure serum creatinine levels, and the pancreas was excised and fixed in 4% paraformaldehyde after sacrificing the rats with Azan staining. Results: A marked increase in systolic blood pressure was observed in SHRsp rats compared with controls (224 ± 12 mmHg vs. 120 ± 8 mmHg, respectively), which was significantly reduced by hydralazine and irbesartan administration (SHRsp+Hyd, 166 ± 12 mmHg; SHRsp+Irb, 180 ± 9 mmHg). There was no significant change in oral glucose tolerance test results in any groups. However, a greater Azan staining area was seen in SHRsp rats compared with controls, and irbesartan significantly decreased the Azan staining of islets in SHRsp rats. Irbesartan also decreased the number of ED1-positive islet cells compared with SHRsp and SHRsp+Hyd rats. Conclusions: We demonstrate islet morphological changes in hypertensive rats, and our data suggest that angiotensin receptor blockers have the potential to prevent islet injury through independent blood pressure-lowering effects.