Carroll A. Handley

Norepinephrine and Epinephrine Effect on Renal Hemodynamics With Particular Reference to the Possibility of Vascular Shunting and Decreasing the Active Glomeruli

Because increasing evidence suggests that renal ischemia resulting from various stress states plays a major role in the etiology of lower nephron nephrosis, the renal hemodynamic effect of continuous infusions of norepinephrine and epinephrine was studied in dogs. The primary response was a decrease in renal blood flow. As the rate of infusion was increased, a progressive decrease in the number of functioning glomeruli followed. Despite the decrease in renal blood flow, there is no evidence to indicate arteriovenous shunting mechanisms.

Some Pharmacological Properties of Three New Mercurial Diuretics.

Summary The compounds, 3–chloromer–curi–2–methoxypropylurea (1347Ex), 3–car–boxymethylmercaptomercuri − 2 – methoxypro–pylurea (1353 Ex), and. 3 – (α–carboxye thylmer–captomercuri) − 2 –methoxypropylurea (1431–Ex), had 3 or 4 times the diuretic potency of meralluride in the dog. Twenty–four and 48 hour mercury excretion rates were comparable to that of meralluride at the same dosage level. Chronic toxicity studies indicated no essential difference between meralluride and the other compounds, if the greater diuretic potency of the new compounds was considered and the dosage adjusted accordingly. Large amounts of 1353Ex and 1431 Ex were infused intravenously without disturbing cardiac function, but the acute cardiac toxicity of 1347Ex, although greater than the other 2 compounds, appeared to be less than meralluride.

Laboratory and Clinical Observations on Mecamylamine as a Hypotensive Agent.

Summary and Conclusions Mecamylamine produced the same cardiovascular and renal hemodynamic effects on dogs as have been previously observed with such autonomic blocking agents as hexamethonium and pento-linium. When given to patients with hypertension, it produced a consistent reduction in blood pressure which was most marked in the upright position. The effect was about equivalent when given orally as when given parenteral^ the average daily dose being approximately 19 mg. The onset of action ranged from 1/2 to 2 hours, and lasted 12 to 48 hours. The response was quite variable from patient to patient, but within the same patient, it was reproducible, thus minimizing one of the chief objections to ganglionic blocking agents for the treatment of hypertension.

The Effect of Adrenergic Blockade and Norepinephrine on Renal and Cardiovascular Hemodynamics Following Hemorrhage

Renal blood flow and other renal functions are depressed when the normotensive animal is made hypertensive by the administration of norepinephrine. By contrast, when the blood pressure is increased to normal with norepinephrine in the animal previously made hypotensive by hemorrhage, renal function and cardiac output increase.

Clinical diuretic studies on three new mercurial compounds

Abstract 1.1. Three new mercurial diuretics, 3-chloromercuri-2-methoxypropylurea (1347Ex), 3-carboxymethylmercaptomercuri-2-methoxypropylurea (1353Ex), and 3-(a-carboxyethylmercaptomercuri)-2-methylpropylurea (1431Ex), have been evaluated on 152 patients. The drugs were given twice per week, intramuscularly, in varying doses to 109 patients in the outpatient clinic. The diuretic effects of the drugs were compared to the previous responses of the patients to Mercuhydrin. 2.2. In doses equivalent to 10 and 20 mg. Hg of the experimental diuretics, none offered much of an advantage over Mercuhydrin. This is apparently due to the fact that a threshold amount of mercury must be presented to the renal tubules before any diuresis results, regardless of the mercurial compound. From clinical observations this amount appears to be between 10 and 20 mg. Hg. 3.3. When larger doses of the experimental diuretics (equivalent to 40 mg. Hg) were administered, they appeared to have a higher order of potency than Mercuhydrin when compared on the basis of mercurial content. When evaluated on a clinical basis, this ratio was greater than 2:2 and appeared to be about the same for all of the drugs under investigation. 4.4. Electrolyte studies were done on forty-three hospitalized patients. After all three of the diuretics there was a marked increase in urine and sodium excretion. The concentration of sodium per unit volume of urine was also increased. Potassium excretion was increased but this was erratic. 5.5. Of the three experimental diuretics studied, 1347Ex exhibited an increase in sodium and water excretion of highest order of statistical significance.

Effect of thiols on mercurial diuresis.

Summary The diuretic action of organic mercurials or inorganic mercury compounds is prevented or abolished by certain thiols. Of the compounds tested? Bal was the most effective, followed by thioglycolic acid, glutathione, and methylene blue in decreasing order of activity. Cysteine had very little effect.

Effect of Chronic Administration of Mercurial Diuretics on Glomerular Filtration in the Dog.

Summary Mercurial diuretics administered intravenously in chronic dosage to dogs reduced the glomerular nitration rate as measured by the creatinine clearance. This reduction in glomerular filtration rate was found to be temporary in most dogs that did not have severe symptoms of mercury poisoning. Thiomerin, when administered intravenously in comparable chronic dosage to the dog, was found to be of higher toxicity than either Mercuhydrin or Merthyl, as indicated by reduced creatinine clearances, and other signs of mercury poisoning.

Xanthine and Mercurial Diuretics and Renal Tubular Transport of Glucose and P-aminohippurate in the Dog.∗:

Summary Mercuhydrin, salyrgan and theophyllin, in diuretic doses, do not interfere with the renal tubular transfer of glucose or p-aminohippurate in the dog.

Renal function during viomycin administration to dogs.

Summary Daily doses of 15-60 mg/kg of Viomycin administered for a period of 6 months did not appear to produce any evidence of renal toxicity as estimated by renal function studies (clearances). There were no serious alterations of the concentrations of serum sodium and potassium. These data suggest that the renal toxicity and altered electrolyte metabolism associated with Viomycin therapy may not be as serious as the earlier observations indicated. Therefore, we believe that further use of Viomycin with careful observations for signs of renal toxicity is indicated, particularly in patients unresponsive to the other more effective therapeutic approaches.

Chromatography Studies of the Excretion Products after Meralluride Administration in Normal Subjects and Cardiac Patients

Separation of the urinary excretory products of the organomercurial diuretic, meralluride (Mercuhydrin) has been possible using adsorption chromatography. Practically all of the mercury is excreted in a form closely resembling the administered meralluride. Most of the excretion occurs within the first 6 hours in both cardiac patients and normal subjects. The amount of mercury excreted as degradation products is insufficient to produce diuresis. Therefore, it is concluded that the diuretic action of meralluride depends on the specific organic mercurial molecule.