Neuroprotective effect of treatment with calcium antagonists on hypertensive retina.
The influence of hypertension and of treatment with the dihydropyridine-type Ca2+ antagonists lercanidipine, manidipine, nicardipine, and nimodipine and with non dihydropyridine-type vasodilator hydralazine on retinal nervous and glial fibrillary acidic protein (GFAP) immunoreactive astrocytes were investigated in male spontaneously hypertensive rats (SHR). Normotensive Wistar-Kyoto (WKY) were used as normotensive references group. Treatment of animals with oral equi-hypotensive doses of the above compounds started at 14 weeks of age and lasted for 12 weeks. Microanatomical analysis was extended to samples of frontal cortex and occipital cortex used as reference tissue. Different compounds investigated decreased to a similar extent systolic blood pressure values with the exception of nimodipine that in spite of the high dose used exerted a less pronounced hypotensive activity. Morphological changes including reduced thickness of retina and of inner plexiform, outer nuclear and layer of inner and outer segments plus outer limiting layer, and loss of ganglionic neurons were observed. GFAP-immunoreactive astrocyte hypertrophy was also found in control SHR. These phenomena were countered by treatment by treatment with dihydropyridine-type Ca2+ antagonists and to a lesser extent by hydralazine. The different Ca2+ antagonists tested exerted a similar protective effect on retinal, but not on brain neurons. The sensitivity of retina and cerebral cortex to anti-hypertensive treatment may be related to a different density of L-type Ca2+ channels in structures investigated or to kinetic reasons. The demonstration of a neuroprotective effect of Ca2+ antagonists on retina of SHR suggests that these compounds might protect to a some extent retina from hypertensive injury.
Sabbatini
Maurizio
M
Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, 62032 Camerino, Italy.
Tomassoni
Daniele
D
Di Tullio
Maria Antonietta
MA
Amenta
Francesco
F
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology / Q000627:therapeutic use; D009553:Nimodipine / Q000494:pharmacology / Q000627:therapeutic use; D009578:Nitrobenzenes; D009798:Ocular Hypertension / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015356:Retinal Artery Occlusion / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D006830:Hydralazine; D009553:Nimodipine; C054218:manidipine; C038806:1,4-dihydropyridine; D009529:Nicardipine; C060343:lercanidipine