PST 2238: A New Antihypertensive Compound That Modulates Renal Na-K Pump Function Without Diuretic Activity in Milan Hypertensive Rats
| Autor: | E. Minotti, Mara Ferrandi, Paolo Barassi, Isabella Molinari, Liliana Duzzi, Patrizia Ferrari, Giuseppe Bianchi |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Blood Pressure Kidney Oral administration Internal medicine Renin–angiotensin system medicine Animals Androstanols Na+/K+-ATPase Pharmacology Reabsorption business.industry Lipid metabolism Diuresis Rats Hydrochlorothiazide Endocrinology Blood pressure Renal physiology Hypertension Sodium-Potassium-Exchanging ATPase Diuretic Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Cardiovascular Pharmacology. 40:881-889 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-200212000-00009 |
| Popis: | PST 2238 is a new antihypertensive compound that is able to correct the molecular and functional alterations of the renal Na-K pump and the pressor effect associated with either alpha-adducin mutations or high circulating levels of endogenous ouabain (EO) in genetic and experimental rat models. Due to the close relationship between renal Na-K pump function and tubular Na reabsorption, PST 2238 was investigated to determine whether it is endowed with diuretic activity and consequently might trigger alterations of the renin-aldosterone system and the carbohydrate and lipid metabolism often associated with chronic diuretic therapy. In Milan hypertensive (MHS) rats, in which hypertension is genetically associated with alpha-adducin mutation, increased tubular Na reabsorption, and hyperactivation of the renal Na-K pump. PST 2238 reduced blood pressure and normalized the renal Na-K pump activity at oral doses of micro g/kg, but did not induce, either acutely or chronically, any diuretic activity or hormonal or metabolic alterations. In contrast, HCTZ, given to MHS rats orally at 40 mg/kg, although it displayed diuretic activity and reduced the renal Na-K pump activity, did not lower blood pressure and caused hyperactivation of the renin-aldosterone system, hypokaliemia, and hyperglycemia. The findings lead to the conclusion that PST 2238 is a new antihypertensive compound that normalizes the altered function of the renal Na-K pump associated with hypertension in rat models, but that it is devoid of diuretic activity and does not induce the diuretic-associated side effects. |
| Databáze: | OpenAIRE |
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