The effects of propylbutyldopamine ( PBDA ), an analog of dopamine lacking significant vasoconstrictor effects, were examined in seven patients with essential hypertension. Cardiovascular hemodynamics, renal plasma flow, urinary sodium excretion, and the renin-angiotensin-aldosterone system were examined during PBDA infusion both before and after administration of low (8 micrograms/kg) and high (40 micrograms/kg) doses of the dopamine receptor antagonist metoclopramide. Infusion of PBDA at a rate of 20 micrograms/kg/min lowered mean arterial pressure from an average control value of 112 +/- 4 to 94 +/- 3 mm Hg during the last 5 minutes of infusion (p less than 0.01), and increased effective renal plasma flow from 330 +/- 22 ml/min to 591 +/- 46 ml/min (p less than 0.01). Changes in heart rate (+ 16% +/- 5% increase from control values of 77 +/- 3 bpm), urinary sodium excretion (+ 13% +/- 5% increase from control value of 121 +/- 11 muEq/min), plasma renin activity (+ 23% +/- 15% increase over control value of 1.3 +/- 0.3 ng angiotensin I/ml/hr), and plasma aldosterone (+ 26% +/- 12% increase over control value of 17 +/- 6 ng/dl) accompanied PBDA infusion. Pretreatment with metoclopramide at a dose of 8 micrograms/kg prior to PBDA infusion partially blunted the blood pressure reduction produced by PBDA alone (-10% +/- 8% vs -20% +/- 4% compared to control values, p less than 0.1) but had no effect on PBDA -induced increases in renal plasma flow (+ 179% +/- 15% vs + 179% +/- 9% compared to control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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Noradrenergic mediation of experimental cerebrovascular spasm.

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Animals↗

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Adrenergic blockade of hypocapnic cerebral arterial constriction.

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Adrenergic alpha-Antagonists↗

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The development of modern intracranial aneurysm surgery.

This history of the steps leading to the modern surgical treatment of intracranial aneurysms begins some 200 years ago when it was found that cervical carotid artery ligations (for trauma) could be tolerated. This discovery led, early in the 1800's to the use of carotid ligation for the treatment of carotid-cavernous fistulas and eventually for the treatment of intracranial saccular aneurysms. The era of modern intracranial surgery for aneurysms began after Moniz introduced cerebral angiography in 1927. The first trapping procedure (for a carotid-cavernous fistula) was performed in 1932, and the first successful planned intracranial operation for a saccular aneurysm was reported in 1933. Subsequent developments are chronologically cited, together with mention of methods now obsolete.

Carotid Arteries↗

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Antihypertensive effect of fosinopril, a new angiotensin converting enzyme inhibitor: findings of the Fosinopril Study Group II.

In a double-blind study, after a four- to six-week placebo period, 418 patients with mild to moderate hypertension were randomly assigned to receive 5, 10, 20, or 40 mg of fosinopril or matched placebo orally once daily for four weeks. Seated diastolic blood pressure was determined 24 hours after the most recent dose. For patients with an inadequate blood pressure response after four weeks, doses were doubled during the second four weeks, and hydrochlorothiazide was added during the final four weeks. The patients showed a significant, consistent antihypertensive response in seated and standing systolic and diastolic blood pressures after four weeks of 20 or 40 mg of fosinopril; both dosages produced similar responses. The results indicate that the dose level of fosinopril required to treat uncomplicated mild to moderate hypertension ranges from 5 to 40 mg taken once daily. Treatment was discontinued in 3% of the fosinopril patients and in 1% of the placebo patients because of side effects. No clinically significant abnormal laboratory test results were reported. Fosinoprilat, the active diacid of fosinopril, is eliminated by both the hepatobiliary and renal routes, which suggests that fosinopril may be particularly useful in the treatment of patients with impaired kidney or liver function and of elderly patients.

Adult↗

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Doxazosin: a new approach to hypertension and benign prostatic hyperplasia.

Doxazosin, a selective alpha 1-adrenoceptor antagonist, is an established first-line antihypertensive agent that is being introduced for the management of benign prostatic hyperplasia. Hypertension and benign prostatic hyperplasia are linked by the sympathetic nervous system, which has an aetiologic role in both conditions. The alpha 1-adrenoceptor is a mediator of increased tension, both in vascular and prostatic smooth muscle. Studies have shown that doxazosin, through its balanced action on alpha 1-adrenoceptor subtypes, reduces blood pressure and improves other risk factors for coronary heart disease, such as lipid profile, insulin sensitivity, left ventricular hypertrophy, platelet aggregation and fibrinolysis. Data are now accumulating to show that doxazosin improves urinary flow rates and symptoms in patients with benign prostatic hyperplasia. These effects have been demonstrated in controlled clinical studies, within weeks, and long term. Since hypertension and benign prostatic hyperplasia are widespread and often undiagnosed in the community, particularly with increasing age, doxazosin may be a particularly appropriate therapy for the considerable number of older men with both conditions.

Adrenergic alpha-Antagonists↗