Treatment of chronic orthostatic hypotension with ergotamine.

The acute and chronic effects of ergotamine were examined in four patients with chronic orthostatic hypotension. Chronic oral administration of ergotamine tartrate produced significant increases in standing blood pressure and marked clinical improvement, without appreciable recumbent hypertension. The blood pressure increases were not associated with significant changes in plasma norepinephrine or plasma renin activity. No major toxicity was observed at doses of 2-6 mg/day over treatment periods of 3-18 months. Hemodynamic studies on the effects of i.v. ergotamine tartrate (0.25-0.50 mg) revealed that the ergotamine-induced increase in blood pressure in the supine position was associated with an increase in total peripheral resistance (from 1616 +/- 165 to 2574 +/- 583 U) without a change in cardiac output. During 45-60 degrees upright tilt, ergotamine increased both total peripheral resistance (1801 +/- 296 to 3262 +/- 1107 U) and cardiac output (2.42 +/- 0.46 to 3.34 +/- 0.54 l/min). Forearm plethysmographic studies revealed decreased forearm blood flow and venous volume and increased vascular resistance with ergotamine. The orthostatic hypotensives had more platelet alpha-receptors (390 +/- 31 receptors/cell) than the control subjects (234 +/- 17 receptors/cell). The increased receptor level was associated with abnormally low circulating levels of norepinephrine and increased pressor responsiveness to infused norepinephrine in three of the four patients. Chronic ergotamine therapy appeared to reduce platelet alpha-receptor number to normal. The results indicate that ergotamine is of value in certain patients with chronic orthostatic hypotension and that the blood pressure effects are related to vasoconstriction in both arterial and venous beds.