Both underproduction and overproduction of nitric oxide (NO) could lead to various eye diseases. It is known that endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are activated in normal tissues to produce NO for physiological functions. Thus, underproduction of NO results in various eye diseases which could be corrected by providing NOS substrates or NO donors to lower the intraocular pressure, increase ocular blood flow, relax ciliary muscle, etc. On the other hand, immunological NOS (iNOS) is inducible only in pathological conditions by endotoxins, inflammation, and certain cytokines, such as interleukin-1 (IL-1), IL-6, TNF (tumor necrosis factor) and the like. Once induced, iNOS will produce large amounts of NO for long periods of time, so that NO is converted into NO2, nitrite, peroxynitrite and free radicals to induce pathophysiological actions, such as optic nerve degeneration and posterior retinal degeneration lesion, which lead to glaucoma, retinopathy, age-related macular degeneration (AMD), myopia, cataracts and uveitis. To treat/prevent these eye diseases, inhibitors of iNOS activity and/or iNOS induction could be tried.
The cardiovascular pharmacology of two Chinese herbs, Salvia miltiorrhiza (SM) and Panax notoginseng (Burk) F. H. Chen (PNG) were studied both in vivo and in vitro. Extracts of both herbs suppressed systemic blood pressure in albino rats and rabbits, an effect which was blocked or reversed by atropine, propranolol, and chlorpheniramine plus cimetidine. This reversed hypertension was blocked by phenoxybenzamine. These results indicate that these herbs have multiple effector sites in the cardiovascular system. This could be due to an increased utilization of extracellular calcium ions since the activity of SM on isolated blood vessels of rabbits was enhanced by 2 mM Ca++. The effects of aqueous extract of SM and purified active principles of SM (tanshinones) on rat and rabbit blood vessels in vitro were very similar both qualitatively and quantitatively. Both caused vasodilation of coronary arteries at all concentrations tested but induced vasodilation of renal, mesenteric and femoral arteries only at low concentrations. At higher concentrations, vasoconstriction was induced in these vessels. These results indicate that an economical decoction of SM is as efficacious as the more expensive isolated tanshinones. Both SM and PNG would be useful as antianginal agents since they dilate coronary vessels. Their use in hypertension is questionable since they induce both vasodilation and vasoconstriction depending on dose and target vessel.
Cardiovascular actions of S. miltiorrhiza (SM) were studied on systemic blood pressure in the rat. Langendorff cardiac preparation in the guinea pig, and four types of vasculature in the dog, including coronary, renal, femoral, and mesenteric arteries. SM induced dose-related hypotension without changing heart rate. The hypotension was antagonized by atropine, propranolol, and chlorpheniramine plus cimetidine. In the isolated whole-heart preparation, SM increased coronary blood flow significantly for 15 min and positive inotropic action for 3 min after pulse injection. SM relaxed all arteries at low concentration (3.0 mg/ml) and contracted all but the coronary artery at higher concentration (10.0 mg/ml). The coronary artery relaxed at all doses of SM tested.
The effect of timolol on the active transport system in the iris root-ciliary body of rabbits was studied to elucidate the action mechanism of timolol. Neither Na+-K+-adenosine triphosphatase (ATPase) nor Mg++-ATPase was inhibited by timolol at 1 × 10––4 M concentration. None of the energy production parameters (oxygen consumption, glucose metabolism, and lactic acid formation) was inhibited by timolol either. Further, the biosynthesis of prostaglandins E2 and F2α was not affected by timolol at 1 × 10––3 M. The blood flow to the eye was measured with a 85Sr-microsphere method. It was found that the blood flow in the iris root-ciliary body and choroid was significantly reduced by a topical application of 0.25% timolol. The dopamine concentration in the iris root-ciliary body was reduced by timolol at 1 × 10––5 M concentration. Neither epinephrine nor norepinephrine concentration was altered by timolol. The results indicate that timolol reduces the rate of aqueous humor formation through reduction of blood flow to the ciliary process rather than via the inhibition of the active transport system or that of prostaglandin biosynthesis.
Ischemic retinopathy and age-related macular degeneration are the leading ocular diseases that cause blindness. The etiology of these diseases is due in part to the reduction of blood flow in the retina and/or choroid. Crocin analogs isolated from Crocus sativus L. were found to significantly increase the blood flow in the retina and choroid and to facilitate retinal function recovery. Increased blood flow due to vasodilation presumably improves oxygenation and nutrient supply of retinal structures. These results indicated that crocin analogs could be used to treat ischemic retinopathy and/or age-related macular degeneration. It was noted that disaccharide analogs of crocin, such as crocin-1 and crocin-2, were less potent than monosaccharide analogs of crocin, such as crocin-3 and crocin-4, constituting an interesting structure-activity relationship.
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