Earlier reports (1-3)l described the ability of the nonapeptide SQ 20881 ( 150 mm Hg. 1 The initial demonstration of use d this class of peptides in ameliomtimg renal hypertension in three different models was first dexnibled by E. M. Krieger et al. [Lancet i, 2169 (1971)l for thle pentapeptide BPP,,.(b) Goldblatt-type hypertension. The left renal arteries of etherized rats of the Carworth Farms Nelson strain (CFN) were partially constricted with clips (id. 0.22 mm) fashioned from silver ribbon fn a modilfication of the technique of Goldblatt (10). The right renal arteries were left unclipped. In some of these animals, the right kidneys were removed ("l-kidney" Goldblatt model) during the same operation. These rats were used in experiments with SQ 20881 6-21 days after operation, again after plethysmographic evidence of hypertension.(c) Hypertension induced by aortic ligation. Ligation of the aorta with surgical silk between the origins of the renal arteries (1 1) was performed in etherized rats of the HSD strain. The animals were used in experiments with SQ 20881 6-8 days after operation when they had become hypertensive, as indicated by plethysmographic readings.(d) Hypertension induced by unclamping an acutely clamped renal pedicle. Plastictipped hemostatic forceps were applied to both renal pedicles of HSD rats after they had been anesthetized (see below). Six hours ,thereafter, the left renal pedicle was unclamped and iv infusion of test compound was begun as soon as the resultant hypertension had stabilized (about 10 min after unclamping ) ( 12).Anesthesia was induced by the administration of sodium pentobarbital, 40 mg/kg, ip, in Grollm...
SUMMARYThe relative roles of tbe sympathetic nerrous system and renin-angiotefisin system in the development of two-kidney renal hypertension were studied using four groups of rats: Group I = vehicle control; Group II = 6-OH-dopamine (2 weeks prior to renal clipping then weekly throughout the study); Group III = adrenal medullectomy plus vehicle; Group IV = o-OHndopamlne plus adrenal medullectomy. Six weeks after clipping of a single renal artery, plasma renln activity (PRA) was comparably elevated in all groups. However, mean blood pressure (MBP) of Group II was lower than that of Group I controls (154.
provide evidence to support the hypothesis that triamterene acts in the distal tubule to reduce Na reabsorption. While this drug acts in the same area of the tubule as aldosterone and causes effects on sodium reabsorption opposite to those attributed to aldosterone( 9 ) , competitive inhibition cannot be inferred.The fact that triamterene causes a natriuresis in adrenalectomized rats and dogs indicates that the drug acts by other mechanisms than aldosterone antagonism.There were no consistent changes in urine flow rate, free flow urine Na concentration, and proximal urine Na concentration in 4 experiments where stop flow studies were done before and after triamterene. While proximal tubular events are not as easily assessed by the stop flow method (6), there is no evidence to support the idea of a proximal tubular action of the drug.Summary. The pteridine compound triamterene was studied in l l dogs using the stop flow method. These data support the hypothesis that the site of action of triamterene is the distal tubule of the kidney and that triamterene produces its natriuretic effect by reducing Na reabsorption in this area.No evidence was obtained for a proximal renal tubular effect.The authors wish to thank bt. W. S. Wilde for helpful criticism on stop flow and for the use of laboratory facilities and grant support in his absence.
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