Furosemide

Abstract: A B S T R A C T Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB2 and renal prostaglandin (PG) and prostacyclin (PGI2) production. We measured, by radioimmunoassay, serum TXB2 levels after whole blood clotting and urinary excretion of PGE2, PGF2a, and 6-keto-PGF,a, before and after single or repeated oral aspirin doses given to 46 healthy subjects. Single doses of 6-100 mg aspirin resulted in a linear (r = 0.92, P < 0.01) inhibition of platelet TXB2 production, ranging from 12 to 95% after 24 h. A daily dose of 0.45 mg/kg given for 7 d produced a cumulative and virtually complete inhibition of platelet TXB2 production, without significantly reducing the urinary excretion of PGE2, PGF2a, and 6-keto-PGF,a in both healthy men and women. The platelet inhibitory effect of this regimen was maintained unaltered throughout 1 mo of therapy, with no evidence of cumulative inhibition of renal PGsynthesis. Moreover, furosemide-induced renal PGI2 synthesis and renin release were unaffected by chronic low-dose aspirin. Following cessation of aspirin therapy, platelet TXB2 production returned toward control values at a similar rate as after a single higher dose. We conclude that in healthy subjects: (a) aspirin causes a dose-dependent inhibition of platelet TXA2 production, with no obvious sex-related difference; (b) the inhibitory effect of daily low-dose aspirin is cumulative on platelet TXA2 but not on renal PG-synthesis; (c) during chronic low-dose aspirin therapy, renal PGI2-producing cells are readily activable by furosemide at a time of virtually complete suppression of platelet cyclooxygenase activity.

Abstract: Sensitivity and resistance to the effects of sodium were evaluated in normotensive and hypertensive humans by two approaches. Blood pressure was measured after an intravenous infusion of 2 L of normal (0.9%) saline and after sodium and volume depletion induced by a low sodium diet and furosemide administration in 378 normal volunteers and 198 subjects with essential hypertension. Those in whom mean arterial blood pressure decreased by at least 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, and those with a decrease of 5 mm Hg or less (including an increase in pressure) were considered sodium-resistant. The second study utilized the blood pressure response to modest dietary sodium restriction in 74 normotensive subjects to identify sodium sensitivity and resistance. In both studies the responses were heterogeneous. In the first study significantly more hypertensive subjects were sodium-sensitive, as compared with those in the normotensive group (p less than 0.001). Plasma renin activity (low, normal, or high) did not predict sodium responses. In both groups sodium-sensitive individuals were significantly older (p less than 0.001) and had lower baseline renin values than sodium-resistant subjects. Factors related to the change in mean arterial blood pressure after sodium and volume depletion included baseline pressure (r = -0.54, p less than 0.001) and age (r = -0.16, p = 0.002 in the normotensive group; r = -0.28, p less than 0.001 in the hypertensive group). The response to dietary sodium restriction was also correlated with baseline pressure (r = 0.61, p less than 0.001) and the initial urinary sodium excretion (r = 0.27, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)