The ability of l-dopa and dopamine to modulate renal vascular responses to norepinephrine (NE, 50-150 ng) was examined in isolated Tyrode-perfused kidneys from male Sprague-Dawley rats. Renal pressor responses to bolus injections of NE were constant during saline infusion. In contrast, l-dopa (15 micrograms/min and 75 micrograms/min) and dopamine (15 micrograms/min) infusions that did not alter baseline perfusion pressure increased pressor responses to NE significantly. Concomitant infusion of the aromatic l-amino-acid decarboxylase inhibitor carbidopa (20 micrograms/min) suppressed the ability of l-dopa (75 micrograms/min) but not dopamine to enhance renal pressor responses to NE. The pressor potentiation of NE did not appear to be the result of a general musculotropic effect or altered alpha-1 adrenoreceptor activity since increased vasoconstrictor responses to phenylephrine (PE) and serotonin (5-HT) were not observed. Infusions of cocaine (15 micrograms/min) enhanced the renal pressor effects of NE but not PE in similar fashion to l-dopa and dopamine. In the presence of cocaine, l-dopa did not potentiate NE constriction further. These results suggest that endogenous or exogenous dopamine in the kidney may affect neuronal NE uptake to enhance its renal vascular effects.

Animals↗

PubMedDate not supplied

The role of adrenergic drugs in antihypertensive therapy.

Abnormalities in the adrenergic system are believed by some to be a major contributing factor to primary hypertension, which may explain the increasing clinical usefulness of drugs that affect the adrenergic system. The clinical effects of drugs in this class can be predicted by the location of the alpha or beta receptors that are activated or inhibited by the drug. With the wide range of antihypertensive drugs now available, including diuretics and vasodilators as well as adrenergic agents, it is possible to individualize treatment in ways more appropriate than the traditional stepped-care approach.

Age Factors↗

PubMedDate not supplied

Effect of lovastatin on serum lipids in patients with nonfamilial primary hypercholesterolemia.

The effect of lovastatin on serum lipids and its tolerability in patients with non-familial primary hypercholesterolemia (type II-A and type II-B) during a six-month period were evaluated in this open-label study. Thirty-eight patients were enrolled in the study; tolerability was assessed in all 38 patients. Thirty patients completed the study, and the effect of lovastatin on serum lipids in these patients was assessed. Some patients had been treated for hypercholesterolemia with long-term dietary and other non-pharmacologic means before entry into the study. All patients were unresponsive to a six-week program of intensive dietary therapy and other nonpharmacologic treatment to lower their blood cholesterol levels before receiving lovastatin. While maintaining intensive dietary therapy, administration of lovastatin was instituted at a dosage of 20 mg/day, which was increased by 20-mg increments monthly, as necessary, to a maximum of 80 mg/day. In an effort to achieve goal levels of low-density lipoprotein cholesterol (LDL-C), ten patients received a daily dosage of 20 mg, 12 patients received 40 mg, seven patients 60 mg, and one patient 80 mg. Twenty-nine of the 30 patients achieved significant lowering of serum levels of total cholesterol (TC), LDL-C, and apolipoprotein (apo) B-I; this was demonstrated after the first month of therapy with lovastatin and was maintained throughout the six-month treatment period. One patient failed to demonstrate lowering of these serum lipids, despite receiving the maximum recommended dosage of lovastatin of 80 mg/day. Comparative measurements of serum lipids during dietary therapy alone and after six months of diet plus lovastatin therapy were as follows: TC, 289 +/- 5 versus 216 +/- 9 mg/dl (P less than 0.0005); LDL-C, 206 +/- 4 versus 141 +/- 5 mg/dl (P less than 0.0005); and apo B-I, 112 +/- 3 versus 89 +/- 2 mg/dl (P less than 0.0005). Serum levels of very-low-density lipoprotein cholesterol (VLDL-C) and triglycerides decreased slightly during lovastatin therapy, but the changes were not statistically significant. There were slight but statistically insignificant increases in serum levels of high-density lipoprotein cholesterol (HDL-C), apo A-I, and apo A-II.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMedDate not supplied

Alpha 1-blockade for the treatment of hypertension: a megastudy of terazosin in 2214 clinical practice settings.

The purpose of this study was to evaluate the effects of the alpha 1-blocking agent terazosin on blood pressure (BP) and blood lipids in a large, variant population of patients with hypertension. A total of 16,917 patients with hypertension were evaluated at 2214 primary and community care facilities; 7808 of these patients had not been treated previously for hypertension; 3928 were switched to terazosin from another antihypertensive agent; and 5181 received terazosin in addition to an agent that had not controlled their hypertension. Terazosin produced highly significant reductions in systolic (-18.2 +/- 0.2 mm Hg) and diastolic (-13.2 +/- 0.1 mm Hg) BP when used as monotherapy (mean dose, 3.1 mg; range, 2 to 10 mg) without causing a significant increase in heart rate. Equal antihypertensive efficacy was demonstrated in men, women, blacks, and whites of all ages, with particular benefit to elderly patients (> or = 65 years of age) with systolic hypertension. Comparative studies indicated that terazosin had equal antihypertensive efficacy in combination with diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Patients who had not responded to monotherapy with one of these classes of antihypertensive drugs showed significant reductions of BP after terazosin, in the following average doses, was added to diuretics, 3.1 mg; beta-blockers, 3.4 mg; calcium channel blockers, 3.3 mg; and ACE inhibitors, 3.4 mg. Terazosin produced highly significant reductions in blood levels of total cholesterol (-5.0%), triglycerides (-6.1%), and low-density lipoprotein cholesterol (-7.6%) without change in high-density lipoprotein cholesterol when used as monotherapy. Similar favorable effects on blood lipid levels were demonstrated when terazosin was used in combination with all other classes of antihypertensive drugs. The greatest reductions in blood cholesterol (-9.2%) were observed among patients with hyperlipidemia (total cholesterol > or = 240 mg/dL). Terazosin maintained its antihypertensive efficacy and was well tolerated by patients with a variety of concomitant diseases, including congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, benign prostatic hyperplasia, diabetes, and obesity. Adverse effects occurred in 17.9% of patients and caused 2.2% to drop out of the study. The most frequent adverse effects were dizziness (4.8%), headache (2.5%), and asthenia (2.4%). Only 0.4% suffered syncope and 0.2% impotence. These data demonstrate the usefulness of terazosin as monotherapy or add-on therapy for treatment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗