Abstract
Purpose :
Systemic hypertension engenders high ocular perfusion pressure (OPP); however extended periods of hypertension may compromise retinal autoregulation such that blood flow may not be adequately maintained during fluctuations in blood pressure (BP) and intraocular pressure (IOP). We considered the effect of an experimental model of chronic hypertension on retinal autoregulation in response to an acute BP challenge in rats.
Methods :
Anaesthetised (60:5mg/kg ketamine:xylazine) adult (24 weeks old) Long Evans rats were implanted with Alzet osmotic minipumps (2ML4) for 12 weeks to induce chronic hypertension. The hypertensive group (n = 10) received a subcutaneous Angiotensin II infusion (150ng/kg/min) and the normotensive group received the saline vehicle only (n = 8). Systolic BP was measured weekly in awake rats (tail cuff sphygmomanometry). After 12 weeks of hypertension, retinal arteriole diameter was assayed (Andor sCMOS camera) during acute BP manipulation induced with intravenous infusion of Sodium Nitroprusside) (0.6mg/mL, 0.003-0.008mL/min, BP reduced to approximately 50mmHg over 15 minutes). The vasodilatory capacity of retinal arterioles during low BP was used as an index of autoregulatory capacity. Ophthalmic artery and aorta tissues were sectioned (Gomori Aldehyde Fuchsin staining) to assess the effect of 12 weeks of chronic hypertension on arterial wall:lumen ratio (WLR). Data are presented as mean±SEM.
Results :
Systolic BP was significantly increased in hypertensive (164.8±4.6mmHg) compared to normotensive rats (122.6±2.3mmHg) (p<0.001, RM two-way ANOVA). Aorta (0.4±0.006 vs 0.3±0.005, p<0.001, t-test) and ophthalmic artery (2.1±0.2 vs 1.4±0.2, p = 0.024, t-test) WLR were significantly increased in hypertensive rats. During acute low BP (-32.50 to -62.50mmHg below baseline), significant vasodilation of retinal arterioles was observed in normotensive rats (p<0.001, restricted maximum likelihood analysis). No significant vasodilation was observed in hypertensive rats (p>0.05). A moderate correlation was found between peak vasodilatory capacity and aorta WLR (rs = -0.6, p = 0.009) and vasodilatory capacity and chronic BP integral over 12 weeks (rs = -0.65, p = 0.003).
Conclusions :
Chronic hypertension impairs the retinal vascular response to autoregulation challenge. It would therefore render the eye more susceptible to blood flow compromise during OPP fluctuations which occur during BP and IOP fluctuations.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.