Effects of neuropeptides on the sumatriptan-disturbed circulation in the optic nerve head of rabbits.
The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.
Gaspar
M N
MN
Department of Pharmacology, Institute of Biomedical Research on Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Ribeiro
C A Fontes
CA
Cunha-Vaz
J G
JG
Macedo
T R A
TR
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008845:Microinjections; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides / Q000494:pharmacology*; D009900:Optic Nerve / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D018170:Sumatriptan / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C054724:senktide; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin