Effects of indoramin therapy on BP, renal function, and body fluid composition.

Indoramin hydrochloride is a new alpha 1-adrenoceptor antagonist. Eleven hypertensive men in whom the BP was normalized with indoramin underwent assessment of renal function, renal hemodynamics, and body fluid composition following short-term (three to six weeks), long-term (five to six months), and withdrawal (two weeks) therapy. Short-term indoramin therapy produced a 28% increase in glomerular filtration rate, a 24% increase in effective renal plasma flow, and a 31% decrease in renal vascular resistance. Although urine flow rate and free water clearance were unchanged, fractional sodium excretion decreased 38%. Long-term indoramin therapy was associated with qualitatively similar renal effects, but the changes did not achieve statistical significance. Plasma volume was increased only during short-term therapy; however, body weight was increased following both short- and long-term therapy. Indoramin effectively lowers BP without producing deleterious renal effects.

Effects of prazosin therapy on BP, renal function, and body fluid composition.

To our knowledge, the long-term effects of prazosin hydrochloride, an alpha 1-adrenoceptor antagonist, on renal function and body fluid composition have not been previously reported. Fourteen hypertensive men in whom the BP was normalized with prazosin monotherapy, underwent assessment of renal function and body fluid composition following short-term (three to six weeks), long-term (five to six months), and withdrawal (two weeks) therapy. Neither short- nor long-term prazosin therapy had any adverse effect on the glomerular filtration rate or effective renal plasma flow. Renal vascular resistance was decreased 14% during short-term therapy, but not during long-term therapy. Urine flow rate, urine osmolality, free water clearance, and fractional sodium and potassium excretions were statistically unchanged throughout drug therapy. Plasma volume and extracellular fluid volume were increased following both short- and long-term therapy. Long-term prazosin monotherapy effectively lowers BP without resulting in drug tolerance, however, sodium retention probably limits its antihypertensive effectiveness.

Use of the converting enzyme inhibitor enalapril in renovascular hypertension. Effect on blood pressure, renal function, and the renin-angiotensin-aldosterone system.

Thirteen patients were entered into a protocol to assess the safety and efficacy of enalapril (MK 421), 5 to 20 mg b.i.d., and hydrochlorothiazide, 50 to 100 mg daily, for the treatment of renovascular hypertension. Specifically monitored were the effects of therapy on blood pressure and pulse, renal function, and the renin-angiotensin-aldosterone axis. Enalapril and hydrochlorothiazide therapy produced excellent control of blood pressure with no adverse side effects. After approximately 8 weeks of therapy, renal vascular resistance was decreased and no adverse effects on glomerular filtration rate or renal blood flow were noted, except in one patient with a functional unilateral stenotic kidney. Patients receiving enalapril and hydrochlorothiazide showed stimulation of plasma renin activity and suppression of plasma angiotensin II, although the initial degree of suppression was not sustained in all patients during prolonged therapy. Although plasma aldosterone concentration was initially suppressed, the degree of suppression was not sustained. Nine patients have been followed for an additional 6 months; none have experienced further progression of renal disease, as assessed by repeated measurements of glomerular filtration and effective renal plasma flow. These results suggest that combined enalapril and hydrochlorothiazide therapy is safe and effective in the medical management of renovascular hypertension and that blood pressure control may be achieved in the absence of sustained interruption of the renin-angiotensin-aldosterone system.

Effects of enalapril alone, and in combination with hydrochlorothiazide, on renin-angiotensin-aldosterone, renal function, salt and water excretion, and body fluid composition.

Enalapril is a new, oral, long-acting nonsulfhydral angiotensin converting enzyme inhibitor. Thirty-nine patients with primary hypertension were entered into a randomized, double-blind protocol to assess the efficacy of enalapril (10 to 20 mg bid), hydrochlorothiazide (25 to 50 mg bid), or combined drug therapy. Enalapril, either alone or in combination with hydrochlorothiazide, effectively controlled blood pressure. Enalapril monotherapy was associated with an increase in plasma renin activity and a decrease in angiotensin II concentration; in patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2, inulin and para-aminohippurate clearances were markedly improved, without producing adverse effects on salt and water excretion or body fluid composition. Combination therapy was associated with a marked increase in plasma renin activity; however, only those patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2 demonstrated suppression of angiotensin II concentration and marked improvement in inulin and para-aminohippurate clearances. These observations suggest that enalapril, either alone or in combination with a diuretic, has the potential to reverse renal function abnormalities encountered in the hypertensive state.

Antibodies against biotinylated proteins are present in normal human serum.

Antibodies against biotinylated proteins have been identified in 10% of individuals tested (6/60). These antibodies bind readily to biotinylated proteins (50% inhibitory concentration = 0.59 mumol/L) but only modestly to free biotin or biocytin. It is unlikely that any clinical consequences occur as a result of these antibodies, because the affinity for free biotin is too low (50% inhibitory concentration = 0.51 mmol/L) to affect the normal level of free plasma biotin, 0.5 nmol/L. The pathogenesis of this antibiotin immune response is unclear. Repeat testing of several individuals 5 months apart indicated that the antibiotin response was stable. In addition, 51 of the individuals tested for antibiotin antibodies were also examined for antiavidin antibodies. Whereas five were positive for antiavidin, only one individual was positive for both antibiotin and antiavidin antibodies. The presence of an antibiotin antibody is unlikely to affect the in vivo use of biotinylated proteins or cells in human subjects because its affinity for biotinylated proteins is modest and the level of biotinylation for in vivo studies is intentionally low. However, these antibodies may affect clinical or laboratory assays based on the biotin-avidin system where an antibiotin antibody may either positively or negatively affect the specific assay.

Renal function and hemodynamics during treatment with enalapril in primary hypertension.

Thirty-nine hypertensive patients were entered into a randomized, double-blind protocol to assess the effects of enalapril (10-20 mg b.i.d.), or combined enalapril (10-20 mg b.i.d.) and hydrochlorothiazide (25-50 mg b.i.d.) therapy on renal function and hemodynamics. Enalapril, either alone or in combination with hydrochlorothiazide, effectively controlled blood pressure. In patients with an initial inulin clearance less than or equal to 80 ml/min/1.73 m2, inulin and p-aminohippurate clearances were markedly improved toward normal following either drug therapy. The filtration fraction was either unchanged (monotherapy) or increased (combination therapy), suggesting a direct glomerular effect of angiotensin-converting enzyme inhibition. Renal vascular resistance was decreased in all patients. These observations suggest that enalapril, either alone or in combination with a diuretic, has the potential to reverse renal function abnormalities encountered in the hypertensive state.