Monosialoganglioside (GM1) treatment of ouabain-induced retinopathy in the rabbit

The mammalian retina is markedly influenced by cardiac glycosides. When nanomolar concentrations of ouabain are intravitreously injected into the rabbit, the visually evoked response completely disappears within 90 min, while scotopic ERG recordings show a remarkably decreased amplitude of the principal waves. When 33 nmol/kg monosialoganglioside are injected intravenously 30 min before topical intoxication, this functional impairment is significantly reduced. The electroretinographic response shows a limited amplitude reduction, while the cortical potential nerver disappears completely. Histological observations of intoxicated retinas show that a degenerative process begins in photoreceptor outer segment 24 h after the intravitreal ouabain injection. Presently, this process involves both the outer and inner nuclear layers and, finally, the ganglion cell layer. Comparing the intoxicated treated and untreated retinas, no difference is found in the degenerative pattern of the two groups. Autoradiographic studies are also reported to correlate the protective effect of monoganglioside (GM1) on this toxic retinopathy with its preferential accumulation in different retinal tissues

AORTIC RESPONSE TO RELAXING AGENTS IN WATANABE HERITABLE HYPERLIPIDEMIC (WHHL) RABBITS OF DIFFERENT AGE

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4-14 months. Serum cholesterol was elevated (626 +/- 99 mg/100 ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 +/- 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 +/- 0.3 mg/100 mg fresh tissue vs. 0.08 +/- 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03-3 microM) on EC50 noradrenaline precontracted rings was similar in 4-6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7-11- (-35% at maximum) and in 12-14-month-old rabbits (-40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12-14-month-old WHHL rabbits the maximal relaxing response was significantly more elevated than in age-matched N.Z. rabbits (50.1 +/- 2.5% vs. 35.1 +/- 3.2%, respectively). The aortic relaxation to NaNO2 (10 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits

Endothelium-dependent relaxation, cholesterol content and high energy metabolite balance in Watanabe hyperlipemic rabbit aorta.

Functional and metabolic parameters of thoracic aorta from Watanabe heritable hyperlipemic (WHHL) rabbits (aged 11-14 months) were investigated in vitro. The aortic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from age-matched New Zealand rabbits (maximal relaxation: 33 +/- 4% in WHHL vs. 52 +/- 2% in controls: P less than 0.005). ATP relaxant effect (only partially endothelium-dependent) was unimpaired in WHHL aorta, and it was much higher than in controls (maximal response: 63 +/- 6% vs. 37 +/- 3%, respectively; P less than 0.005). The response to NaNO2, an endothelium-independent relaxant, was unchanged in WHHL aortas. Acetylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta (r = -0.62, P less than 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of adenine nucleotides and nucleosides in the aortic tissue of WHHL rabbits was lower than in controls, indicating a loss of energy balance. The results indicate a functional damage induced by genetic hyperlipidemia on endothelium-dependent relaxation and an impairment of energy-rich phosphate metabolism of the aortic wall. The relationship between functional and metabolic parameters is not yet clarified