The therapeutic efficacy of midodrine, an alpha-adrenergic agonist that does not cross the blood-brain barrier, was investigated in a double-blind crossover trial in seven patients with orthostatic hypotension due to autonomic failure. We identified two groups of patients: those in whom upright mean arterial pressure significantly increased (group I, n = 3) and those in whom upright mean arterial pressure decreased (group II, n = 4) during midodrine treatment. Body weight changed in a parallel manner with upright blood pressure, increasing in patients of group I and decreasing in patients of group II (p less than 0.05). Autonomic cardiovascular reflexes were significantly more impaired in patients of group II than in patients of group I. We conclude that midodrine is effective in the treatment of orthostatic hypotension only in those patients with significant preservation of autonomic reflexes. Conversely, in patients with markedly impaired baroreceptor mechanisms, treatment with midodrine may produce extracellular fluid volume depletion and exacerbate orthostatic hypotension.

The effect of methylprednisolone or deoxycorticosterone upon systemic arterial blood pressure and components of the renin-angiotensin system was studied in the rat. Rats maintained on regular diets given methylprednisolone suspension 20 mg/kg body wt demonstrated a significant increase in arterial pressure of + 37 plus or minus 5 mmHg, mean plus or minus SE, over a 2-wk period, whereas those treated with DOC and untreated controls showed no significant change. On normal diets, plasma renin concentration (PRC) of methylprednisolone-treated rats was significantly higher than that of DOC-treated rats. Methylprednisolone treatment also resulted in a significant elevation of plasma renin substrate concentration (PRS). Calculated plasma renin activity (PRA) was highest in methylprednisolone-treated rats, significantly above that of the DOC and no-steroid groups. NaCl supplementation resulted in a significant fall in PRC and PRA in all three groups; however, PRS remained significantly above normal in the methylprednisolone-treated rats. The pressor effect of angiotensin II was slightly increased in methylprednisolone-treated rats. Infusion of [Sar1,Ala8]angiotensin II (P-113) in methylprednisolone-treated rats resulted in a significant fall in diastolic arterial pressure. The results imply that methylprednisolone hypertension in the rat may be in part angiotensin dependent.

No abstract

The effect of ethinyl estradiol (EE2) and dexamethasone (Dex) upon plasma renin substrate (PRS) was studied in rats in relation to sexual maturation and pituitary function. Normal adult rats had large increases in PRS when given either EE2 or Dex. Prepubescent (25-day-old) rats also had a substantial increase in PRS following Dex, but no increase in PRS after EE2. In adult rats, hypophysectomy prevented the rise in PRS due to EE2 but did not prevent the increase in PRS due to Dex. Hepatic estrogen and glucocorticoid receptors were measured in immature and adult rats. Immature rats had markedly reduced concentration of hepatic estrogen receptors (16%), compared with adults. In contrast, glucocorticoid receptor concentration was not significantly different between immature and adult rats. The results indicate that the effect of estrogens and glucocorticoids upon PRS are mediated by pathways that are separable at the hormone receptor level.

No abstract