Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension

• Published in: The American journal of cardiology Vol. 60; no. 4; pp. 303 - 308
• Main Authors: Izzo, Joseph L., Licht, Mark R., Smith, Robert J., Larrabee, Patricia S., Radke, Karen J., Kallay, Michael C.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-08-1987; Elsevier
• Subjects: Adrenergic alpha-Antagonists - therapeutic use; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Body Weight - drug effects; Captopril - therapeutic use; Cardiovascular system; Clinical Trials as Topic; Double-Blind Method; Drug Tolerance; Female; Guanidines - therapeutic use; Hemodynamics - drug effects; Humans; Hypertension - drug therapy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pinacidil; Prazosin - therapeutic use; Sympathetic Nervous System - drug effects; Time Factors; Human; Hypertension; Chemotherapy; Alpha blocking agent; Vasodilator agent; Angiotensin converting enzyme; Enzyme inhibitor; Antihypertensive agent; Cardiovascular disease
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/0002-9149(87)90232-3

Chronic responses of systemic hemodynamics and blood pressure counterregulatory (“pseudo-tolerance”) mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an
α
1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p < 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p < 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p < 0.001 each), whereas captopril decreased supine plasma NE by 12% (p < 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p < 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index.