NEUROTRANSMITTER SYSTEMS IN THE DAHL MODEL OF HYPERTENSION; CHOLINERGIC AND ADRENERGIC INTERACTIONS
Using bidirectional selective breeding procedures, Dahl and his colleagues developed a unique model of experimental hypertension. The model consists of two lines of rats: a salt-sensitive (DS) line that develops severe hypertension when exposed to a high NaCl diet and; a salt-resistant (DR) line that remains normotensive when exposed to the same diet. Both lines remain normotensive on a low NaCl diet. Although Dahl and others have presented compelling evidence that renal factors are importantly involved in the pathogenesis of salt-induced hypertension in DS rats and in the resistance of DR rats, several studies suggest the involvement of central nervous system as well. Exposure to psychological stress can initiate hypertension in he DS rats maintained on a low salt diet and can exacerbate salt-induced hypertension. Peripheral sympathetic factors also appear to participate in the pathogenesis or maintenance of hypertension in the DS line. Takeshita and Mark, for example, found that approximately 50% of the increased vascular resistance in hypertensive DS rats was accounted by augmented neurogenic vasoconstriction. In addition, peripheral sympathectomy with 6-hydroxydopamine prevented salt-induced hypertension in adult DS rats while neonatal sympathectomy, following repeated administration of guanethedine, also blocked the development of salt-induced hypertension in infant DS subjects. The cholinergic system has been implicated in other experimental models of hypertension (e.g., the spontaneously hypertensive rat). However, cholinergic factors in the Dahl rat have not been investigated previously. Receptor binding studies of muscarinic and nicotinic receptors sites were performed in specific brain areas, hypothalamus, medulla and cerebral cortex. DS rats, either normotensive or hypertensive had higher concentrations of muscarinic receptor sites in all the brain areas examined. In addition, they also exhibited higher levels of choline acetyltransferase and cholinesterase activity in all brain areas studied. Pharmacological manipulations of the cholinergic system of DS and DR rats is investigated. Physostigmine (PSTG), a known inhibitor of acetylcholine synthesis was injected in DR and DS rats. At both high and low doses, PSTG produced higher and longer lasting elevations in blood pressure in normotensive DS than in the DR rats. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI
EDWARDS, EMMELINE DORSINVILLE, "NEUROTRANSMITTER SYSTEMS IN THE DAHL MODEL OF HYPERTENSION; CHOLINERGIC AND ADRENERGIC INTERACTIONS" (1983). ETD Collection for Fordham University. AAI8323522.