The Neurogenic Component in the Experimental Hypertensive Rat

Abstract

Experiments were carried out to determine the role of the sympathetic nervous system in maintaining an elevated blood pressure in chronic renal and deoxycortico sterone/NaCl induced hypertension in the rat. Inhibition of sympathetic nerve function by pithing, mecamylamine and reserpine markedly reduced the blood pressure in both normotensive and hypertensive anaesthetised preparations. When anti-hypertensive agents were given to conscious normotensive and hypertensive rats, only frusemide lowered the blood pressure of the hypertensive rat to the level obtained after similar treatment of the normotensive rat. With the Gillespie and Mum preparation [8] the hypotensive action of some of these drugs was independent of their effects on the peripheral sympathetic nervous system.

Further evidence for a central hypotensive action of α‐methyldopa in both the rat and cat

“…The results of the present study demonstrate the ability of a-methyldopa to lower arterial blood pressure in conscious, genetic hypertensive rats. This confirms previous findings in which other types of experimental hypertensive rats were used (Davis, Drain, Horlington, Lazare & Urbanska, 1963 ;Henning, 1969;Ayitey-Smith & Varma, 1970;Finch, 1971). Pretreatment of rats with 6-hydroxydopamine, in doses known to produce a peripheral sympathectomy (Thoenen & Tranzer, 1968;Finch & Leach, 1970), did not prevent the hypotensive effect of a-methyldopa, which is evidence against a false transmitter mechanism for a-methyldopa (Day & Rand, 1963.…”

“…Day & Rand (1963,1964) proposed that a-methyldopa exerts its hypotensive effect by the formation of a-methylnoradrenaline which was assumed to be a less potent transmitter than noradrenaline in the peripheral sympathetic nervous system. However, the finding that treatment with a-methyldopa produces only a moderate impairment of peripheral adrenergic transmission is strong evidence against a * Present address: Pharmacology Department, Roche Products Ltd., Welwyn Garden City, Herts. peripheral false transmitter mechanism (Haefely, Hurlimann & Thoenen, 1967;Henning & Svensson, 1968;Finch, 1971). Furthermore, a-methylnoradrenaline and noradrenaline have been reported to be equipotent pressor agents in both the anaesthetized dog and rat (Trinker, 1971).…”

Cardiovascular reactivity in the experimental hypertensive rat

“…The chief difficulty in comparing the pressor responses of various drugs in normotensive and hypertensive animals is that the initial levels of blood pressure are different and therefore influence the respective pressor responses. In order to overcome this problem all intact preparations were spinalized and after this treatment the blood pressures of normotensive and hypertensive rats were approximately the same (Taquini, 1963;Finch, 1970). The responsiveness to noradrenaline, in both DOCA/NaCl and renal hypertensive rats, was generally increased before and after the administration of desmethylimipramine, which suggests a 'postjunctional' type supersensitivity.…”

A Specific Increase in Cardiovascular Reactivity Related to Sodium Retention in Doca-Salt-Treated Rats

“…There is some evidence that DOCA-salt-treated hypertensive rats may have increased pressor activity in the plasma (Hinke, 1965;Dahl, Knudsen & Iwai, 1969), but there are a number of reports that blood vessels from these hypertensive animals are hyperreactive to a variety of pressor stimuli (Sturtevant, 1956;Hinke, 1965;Beilin, Wade, Honour & Cole, 1970;Finch, 1971a). There are also many reports of hyperreactivity in other types of experimental hypertension, including renal hypertension (Phelan, 1966 ;McGregor & Smirk, 1968 ;Davey & Reinert, 1968) and genetic hypertension (Laverty, 1961 ;Haeusler & Haefely, 1970), and in essential hypertension in man (Doyle & Fraser, 1961;Kaneko, Takeda, Nakajima & Ueda, 1966;Sivertsson & Olander, 1968).…”