Canine retinal arterial and arteriolar dilatation induced by nipradilol, a possible glaucoma therapeutic.
The effects of nipradilol, an ocular hypotensive drug, on isolated canine retinal central arteries and on retinal arterioles in vivo were investigated. Nipradilol (10(-9) to 10(-5) mol/l) produced a dose-related relaxation of the arterial strips contracted with prostaglandin F2 alpha which was not influenced by timolol or indometacin. The median effective concentration of this drug was five times that of glycerol trinitrate (GTN). The nipradilol-induced relaxation in the endothelium-intact strips was not influenced by NG-nitro-L-arginine, a nitric oxide synthase inhibitor, but was abolished by oxyhemoglobin and methylene blue. Treatment with high concentrations of sodium nitroprusside abolished the response to nipradilol, as observed with that to GTN. Retinal arterial strips responded to isoproterenol with a slight relaxation which was depressed by nipradilol. In anesthetized dogs, intra-arterial injections of nipradilol dilated the retinal arterioles in the ocular fundus; the dilator potency was approximately one fifth that of GTN. It is concluded that nipradilol dilates canine retinal arteries in vitro and arterioles in vivo, possibly due to activation of soluble guanylate cyclase and increased production of cyclic guanosine monophosphate that are associated with nitric oxide liberated from the molecule itself in the tissue but not derived from the endothelium and perivascular nerve. Beta adrenoceptor blocking action was determined in the retinal artery.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Kitamura
Y
Y
Uchiyama
M
M
Toda
M
M
Ayajiki
K
K
Toda
N
N
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D005901:Glaucoma / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D012161:Retinal Artery / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D011412:Propanolamines; D014665:Vasodilator Agents; C036089:nipradilol