Novel protein toxin-based strategy for development of cytotoxic T lymphocyte vaccines

Unexplained episodic hypertension, hypotension, or orthostatic intolerance, tachycardia, anxiety, and flushing in 21 patients were investigated for the possibility of hypovolemia by blood volume and individual plasma catecholamines (including autocrine paracrine-born dopamine), determinations baseline, in response to upright posture and catecholamines only during the episodic blood pressure swings. Blood volume was determined by Cr51 fixed to patients' hemoglobin, free norepinephrine, epinephrine, and dopamine with dopamine sulfate following sulfatase hydrolysis, radioenzymatically. The recumbent mean 27.4+/-3% (SE) blood volume decrease from predicted values accentuating to 33.5+/-4% upright was associated with normal baseline plasma free norepinephrine, epinephrine, dopamine, dopamine sulfate, plasma renin activity, and aldosterone with normal mean postural responses from all patients except a hyperresponsive compared to controls (p < 0.04), plasma renin activity increase from 0.657+/-0.1 to 4.47+/-1.8 ng/mL/hr. During the hypertensive, hypotensive, or tachycardic episodes the moderate increase of free norepinephrine and epinephrine (p < 0.04) (but not free dopamine) contrasted with an increase of dopamine sulfate from 2.5+/-0.9 to clearly pathological values of 16.8+/-8.3 ng/mL (p < 0.0003 on % increase of individual values). We conclude that the normal (but to the degree of hypovolemia inappropriately low orthostatism- and episodes-associated sympathetic arousal) is outpaced by considerable episodic dopamine sulfate surges, reflecting extraneuronal dopamine discharge. Whether this increase contributes to the increased natriuresis directly or by inhibiting aldosterone response to renin-angiotensin, perpetuating hypovolemia, remains to be established.