Local action of the renin angiotensin system in the porcine ophthalmic circulation: effects of ACE-inhibitors and angiotensin receptor antagonists.
OBJECTIVE
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.
Meyer
P
P
Department of Ophthalmology, University Hospital, Basel, Switzerland.
Flammer
J
J
Lüscher
T F
TF
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D002924:Ciliary Body / Q000098:blood supply; D004730:Endothelium, Vascular / Q000502:physiology; D005123:Eye / Q000098:blood supply*; D008833:Microcirculation / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D012039:Regional Blood Flow; D012084:Renin-Angiotensin System / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I