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Objective: To compare the safeties and efficacies of IV fenoldopam (FNP) vs sodium nitroprusside (NTP) in severe acute hypertension. Methods: A prospective. randomized, open-label, multimember international trial, at 24 academic medical centers, was conducted. The participants were adult patients (21–80 years of age) who had supine diastolic blood pressures (DBPs) ≥ 120 mm Hg, were capable of written informed consent, and did not have selected exclusion criteria. The subjects were randomized to either FNP or NTP therapy; DBP was titrated to 95–110 mm Hg. or a maximum reduction of 40 mm Hg for very high pressures. Infusions were maintained for at least six hours, then the patients were weaned off the IV therapy and oral medication was started. Measurements included BP, heart rate, and duration of study drug infusion and frequency of side effects or complications. Results: A total of IS3 patients (90 FNP, 93 NTP) were enrolled. Fifteen patients from each arm were excluded from efficacy analysis due to protocol violation. There was no significant difference in baseline characteristics. The two antihypertensive agents were equivalent in controlling and maintaining DBP. Systolic blood pressure (SBP) was reduced to a slightly greater degree for the NTP-treated patients during the initial (0.5–1-hr) study period, and both SBP and DBP were reduced more for the FNP-treated patients in the subset receiving infusions during the 12–24-hour period. The adverse effect profiles of the drugs were similar, as were the times to achieve target pressure, with no clinically relevant difference. Conclusions: For patients who had acute severe hypertension, FNP and NTP were equivalent in terms of efficacy and acute adverse events. Because of a unique mechanism of action, FNP may have advantages in selected subsets of patients. Further studies may be indicated in patient populations with pure “hypertensive emergencies.”

In vitro radiolabeled histamine uptake and metabolism were investigated in abdominal aorta, iliac artery, mesenteric artery and hepatic portal vein of the rat. Histamine uptake was rapid and remained linear over the initial 10 min of the accumulation period. The uptake rate was temperature sensitive with marked reduction in rate at 0 degrees C. The accumulation at 0 degrees C represents nonspecific uptake. The uptake of histamine was observed to be related to the amount of tissue stores of histamine as well as extracellular sodium ion concentration. The only histamine metabolite detected in the vasculature examined was imidazoleacetic acid representing almost 80% of the chromatogram radioactivity. This observation indicates the primary metabolic pathway for histamine in rat vasculature involves the enzyme, diamine oxidase.

Cupreidine (6'-hydroxycinchonine) is a recently synthesized analog of quinidine (6'-methoxycinchonine). Previous studies in mice have shown that quinidine and cupreidine have equivalent antiarrhythmic potencies, whereas the acute toxicity of cupreidine is about 50% less than that of quinidine. Many of the serious adverse effects of quinidine are due to undesirable cardiovascular properties. We have, therefore, compared the effects of the two drugs on blood pressure, heart rate, and peripheral vasodilation in rats, and on myocardial contractility in isolated rabbit hearts at a series of comparable doses. Quinidine produces a more marked bradycardia and depression of blood pressure than does cupreidine. The vasodilation produced by intraarterial administration of quinidine was significantly greater than cupreidine. Furthermore, quinidine elicited a greater negative inotropic effect. Cupreidine exhibited a much more favorable hemodynamic profile than quinidine with regard to the properties that were examined. These results, coupled with the fact that cupreidine has significant antiarrhythmic activity and a lower acute toxicity profile, suggest that this drug may be useful in the therapy of cardiac arrhythmias.