Amlodipine effects on vasomotion in rabbit external ophthalmic artery.
BACKGROUND
In order to understand the role of ocular blood flow in normal and pathological conditions, knowledge of the pharmacological control mechanisms involved in the ocular vascular bed is essential. The present study was designed to investigate the reactivity of the rabbit external ophthalmic artery and its collaterals to amlodipine, in order to answer two questions: (1) What are amlodipine effects upon perfusion pressure and spontaneous oscillations in the in situ perfused rabbit eyes? (2) Can intraarterial amlodipine counteract ET-1 induced vasoconstriction?


METHODS
Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. Vasomotor response curves to intraarterial injections of amlodipine 3 mg/ml followed by phenylephrine 250 microg (group A, n = 6) and to amlodipine 3 mg/ml after an intraarterial injection of endothelin-1 (ET-1) 27 microg/ml (group B, n = 6) were obtained. For statistical analysis, the paired t-test and Fourier analysis of frequency spectrums of spontaneous oscillations were used.


RESULTS
Before any drug administration, spontaneous oscillations were observed in the 12 rabbit models. In group A, amlodipine elicited vasodilation and a decrease in frequency and amplitude of the oscillations. In group B, ET-1 induced an increase in vasoconstrictor tone and vasomotion became more evident. With amlodipine after ET-1, we obtained vasodilation and abolition of the vasospasm.


CONCLUSIONS
Our study has two main conclusions: (1) amlodipine, an L-type calcium channel blocker, caused intense vasodilation and decreased both frequency and amplitude of the spontaneous oscillations observed in the rabbit external ophthalmic artery and its collaterals, and (2) when we applied amlodipine in arteries previously contracted by the administration of ET-1, vascular resistance greatly decreased and spontaneous oscillations were abolished. Since ET-1 levels are increased in several ischemic ocular diseases, amlodipine might be beneficial in these patients, allowing a protective action against vasospasm.
Delgado
Esmeralda
E
Departamento de Clínica, CIISA, Faculdade de Medicina Veterinária de Lisboa, Alameda da Universidade Técnica, 1300-477 Lisbon, Portugal. esmeralda@fmv.utl.pt
Marques-Neves
Carlos
C
Rocha
Isabel
I
Sales-Luís
José
J
Silva-Carvalho
Luís
L
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005583:Fourier Analysis; D008297:Male; D009880:Ophthalmic Artery / Q000187:drug effects* / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects*; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D017311:Amlodipine; D010656:Phenylephrine