Changes in the alpha-adrenoceptors in the medulla oblongata including nucleus tractus solitarii of spontaneously hypertensive rats.
The nucleus tractus solitarii (NTS) is a brain stem center mediating depression of blood pressure. In order to elucidate a possible mechanism for the central regulation of blood pressure, we studied noradrenergic indices in the medulla oblongata, a region including the NTS, in spontaneously hypertensive rats (SHR) as compared with normotensive controls of the Wistar Kyoto strain (WKY) at 12 weeks of age. The medulla oblongata was the only brain region showing a significantly low noradrenaline level in the SHR as compared with WKY rats; the level is also significantly decreased at 8 weeks of age. The alpha 1-adrenergic binding sites, as measured with 2-(2', 6'-dimethoxy) phenoxyethylamine-methylbenzodioxan [3H]WB4101 showed significant increases in KD and Bmax values in medulla oblongata homogenates from rats of both strains from 4-12 weeks after birth, with no significant interstrain difference. On the other hand, the KD and Bmax of the alpha 2-sites, measured by [3H]yohimbine binding, were reduced in SHR as compared to WKY animals, even at 4 weeks after birth when hypertension was not yet apparent. As expected, the relatively selective alpha 2-antagonist, clonidine, was a potent inhibitor of [3H]yohimbine binding but not of [3H]WB4101 binding in these homogenates. The results suggest that some genetic disorder in the alpha 2-adrenergic transmission system in the NTS region may be involved in the development of hypertension in the SHR rats.
D000818:Animals; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007700:Kinetics; D008526:Medulla Oblongata / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004298:Dopamine; D009638:Norepinephrine