Angiotensin II-induced constrictions are masked by bovine retinal vessels.

PURPOSE To unmask the vasoconstricting effect of angiotensin II (Ang II) on retinal smooth muscle by studying its interaction with endothelium-derived paracrine substances. This study focused specifically on determining the changes in vascular diameter and the release of endothelial-derived vasodilators, nitric oxide (NO) and prostaglandin (PG) I2, from isolated retinal microvessels. METHODS Bovine retinal central artery and vein were cannulated, and arterioles and venules were perfused with oxygenated/heparinized physiological salt solution at 37 degrees C. This ex vivo perfused retinal microcirculation model was used to observe the contractile effects of Ang II on arterioles and venules of different diameters. The NO and PGI2 synthase inhibitors, 1-NOARG and flurbiprofen, respectively, were used to unmask Ang II vasoconstriction; the changes in vascular diameters were then measured. Enzyme immunoassays were used to measure the release of cGMP (an index of NO release) and 6-keto-PG-F1alpha (a stable metabolite of PGI2) from isolated bovine retinal vessels. RESULTS Topically applied Ang II (10(-10) M to 10(-4) M) caused significant (P < 0.05) arteriolar and venular constrictions in a dose-dependent manner, with the smallest retinal arterioles (7+/-0.2 microm luminal diameter) and venules (12+/-2 microm luminal diameter) significantly more sensitive than larger vessels. After the inhibition of endogenous NO and PGI2 synthesis by 1-NOARG and flurbiprofen, respectively, the vasoconstriction effects of Ang II became more pronounced. Again, the smallest vessels tested were significantly more sensitive, and synthesis of endothelial-derived relaxing factor (EDRF), therefore, may be most important in these vessels. Vasoactive doses of Ang II (10(-10) M to 10(-4) M) caused a dose-dependent increase in the release of NO and PGI2 from isolated bovine retinal vessels, indicating that the increase in EDRF may nullify direct Ang II-induced vasoconstriction. Interestingly, intraluminal administration of Ang II caused only vasodilation. CONCLUSIONS This study demonstrates that the retinal vascular endothelium acts as a buffer against the vasoconstricting agent Ang II via release of vasodilators NO and PGI2, and the vasoconstriction effects due to Ang II are most prominent in the smallest diameter vessels.