Angiotensin II-induced constrictions are masked by bovine retinal vessels

PURPOSE. To unmask the vasoconstricting effect of angiotensin II (Ang II) o n retinal smooth muscle by studying its interaction with endothelium-derive d paracrine substances. This study focused specifically on determining the changes in vascular diameter and the release of endothelial-derived vasodil ators, nitric oxide (NO) and prostaglandin (PG) I-2, from isolated retinal microvessels. METHODS. Bovine retinal central artery and vein were cannulated, and arteri oles and venules were perfused with oxygenated/heparinized physiological sa lt 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 PGI(2) synthase inhibitors, 1-NOARG and flurbiprofen, respectively, were used to unmask Ang II vasocons triction; the changes in vascular diameters were then measured. Enzyme immu noassays were used to measure the release of cGMP tan index of NO release) and 6-keto-PG-F-1 alpha (a stable metabolite of PGI(2)) from isolated bovin e retinal vessels. RESULTS. Topically applied Ang II (10(-10) M to 10(-4) M) caused significan t (P < 0.05) arteriolar and venular constrictions in a dose-dependent manne r, with the smallest retinal arterioles (7 +/- 0.2 mu m luminal diameter) a nd venules (12 +/- 2 mu m luminal diameter) significantly more sensitive th an larger vessels. After the inhibition of endogenous NO and PGI(2) synthes is bp 1-NOARG and flurbiprofen, respectively, the vasoconstriction effects of Ang II became more pronounced. Again, the smallest vessels tested were s ignificantly more sensitive, and synthesis of endothelial-derived relaxing factor (EDRF), therefore, may be most important in these vessels, Vasoactiv e doses of Ang II (10(-10) M to 10(-4) M) caused a dose-dependent increase in the release of NO and PGI(2) from isolated bovine retinal vessels, indic ating that the increase in EDRF may nullify direct Ang II-induced vasoconst riction. Interestingly, intraluminal administration of Ang II caused only v asodilation. CONCLUSIONS. This study demonstrates that the retinal vascular endothelium acts as a buffer against the vasoconstricting agent Ang II via release of v asodilators NO and PGI(2), and the vasoconstriction effects due to Ang II a re most prominent in the smallest diameter vessels.