Local action of the renin angiotensin system in the porcine ophthalmic circulation: effects of ACE-inhibitors and angiotensin receptor antagonists.

PURPOSE

The renin angiotensin system and endothelium-derived substances are important regulators of the microcirculation. The authors studied the roles of angiotensins (Ang), angiotensin converting enzyme (ACE)-inhibitors, and Ang II-receptor antagonists in the porcine ophthalmic circulation.

METHODS

Isolated porcine ciliary arteries were studied in myographs and the intact porcine eye in a perfusion system at 80 cm H2O perfusion pressure with Krebs-ringer bicarbonate solution (37 degrees C, 95% O2, 5% CO2).

RESULTS

ACE-inhibitors enalaprilat and benazepril (both 10(-5) M) did not change ciliary vascular tone nor flow of perfused porcine eyes. However, enalaprilat or benazepril enhanced the relaxation of ciliary arteries to bradykinin (P < 0.02). In the perfused porcine eye, enalaprilat (10(-5) M) augmented vasodilation to bradykinin (P < 0.02). The bradykinin antagonist Hoe 140 (3 x 10(-7) M) prevented the relaxation of ciliary arteries to bradykinin (P < 0.001), but not to acetylcholine. In perfused eyes, Hoe 140 reduced the vasodilation to bradykinin (P < 0.01). Ang II (10(-8) to 10(-6) M) evoked a contraction of ciliary arteries and was more potent than Ang I. Enalaprilat abolished the effect of Ang I. The AT1-receptor antagonist, valsartan (10(-9) to 10(-5) M; 30 minutes) inhibited the response of ciliary arteries to Ang II, whereas the AT2-receptor ligand CGP 42112 B (10(-7) to 10(-8) M) was ineffective. In the perfused porcine eye, valsartan restored the decrease in flow to Ang II.

CONCLUSIONS

Angiotensins play an important regulatory role in the porcine ophthalmic microcirculation through AT1-receptors. ACE-inhibitors prevents the effects of Ang 1 and augment endothelium-dependent relaxation to bradykinin, which releases nitric oxide through B2 receptors.