Effects of anti-hypertensive treatment on functional and structural components of large artery stiffness and retinal vessel diameters in a rodent model of type I diabetes

Background: Diabetes is associated with cardiovascular risk, increased arterial stiffness, and ocular diseases. Whether large artery stiffness is independently associated with diabetes per se or concomitant hypertension is currently unknown. Aims: To determine whether artery stiffness is independently associated with diabetes or is associated concomitantly with hypertension. Methods: Male, Wistar rats (6 weeks of age) were divided into control (n=8), control with anti-hypertensive treatment (telmisartan, 10 mg/kg/day, n=8), induced diabetes (intraperitoneal streptozotocin, 50 mg/kg, confirmed by blood glucose measurement, n=12) and diabetes with anti-hypertensive treatment (n=12). At 18 weeks, rats were anaesthetized (urethane, 1.3 g/kg) and aortic pulse wave velocity (aPWV, aortic stiffness) was measured invasively across a full range of physiological arterial pressure (intravenous phenylephrine, sodium nitroprusside, 30 μg/kg/min). Retinal artery and venous diameters were measured using a custom microscope/camera assembly. Passive (elastin, collagen) and active (endothelial, smooth muscle function) components of aortic vessel stiffness were quantified using tensile testing and myography. Results: Conscious, systolic blood pressure was high in both control and diabetic animals (142±16 and 132±22 mm Hg, respectively) compared to control and diabetic animals on anti-hypertensive therapy (105±11 and 119±14 mm Hg; P<0.01). Diabetic animals had marginally but significantly lower aPWV across all pressures. Anti-hypertensive treatment decreased aPWV within the low pressure range and increased aPWV within the high pressure range for both controls and diabetic animals. This resulted in increased pressure dependency of aPWV with anti-hypertensive treatment. Retinal venous diameters were greater with diabetes. Anti-hypertensive therapy increased retinal venous diameters but decreased arterial diameters. There was no difference in aortic endothelial dependent or independent vasorelaxation. Sensitivity to phenylephrine (vasoconstriction) was less in diabetic animals (P<0.05). Anti-hypertensive therapy caused a rightward shift in the aortic stress-strain curve (P<0.001). Conclusions: Diabetes appeared to have a small but positive effect on arterial stiffness when studied independently of blood pressure. However, high blood pressure decreased the artery's ability to respond to acute pressure changes, possibly due to remodelling of passive aortic wall components. Retinal venous diameters were greater with diabetes, with anti-hypertensive therapy having different effects on the retinal arteries and veins.