title: Chronic angiotensin-converting enzyme inhibition may improve sodium excretion in cardiac transplant hypertension.
abstract: Cyclosporine-associated hypertension (CAH) may be mediated in part by sodium and volume retention. To investigate this issue, we studied the effects of a calcium antagonist, nitrendipine (NIT, 10-20 mg b.i.d.), and a converting enzyme inhibitor, lisinopril (LIS, 10-20 mg o.d.), on blood pressure (office BP, 24 hr ambulatory BP), excretion of an acute sodium load (200 mmol/2 hr i.v.), glomerular filtration rate (insulin clearance), cumulative dopamine excretion, plasma atrial natriuretic peptide (ANP), and endothelin excretion in 8 patients with CAH after cardiac transplantation in a double-blind, randomized, crossover trial for 6 weeks. Five patients received a diuretic during the trial at a constant dose. Office diastolic BP (DBP) decreased significantly with LIS from 97 +/- 6 to 87 +/- 9 mmHg and with NIT from 96 +/- 7 to 92 +/- 12 mmHg. Ambulatory 24 hr DBP decreased significantly from 96 +/- 7 mmHg to 86 +/- 10 mmHg (LIS) and to 84 +/- 11 mmHg (NIT). Ambulatory DBP during the day was lowered significantly from 98 +/- 11 mmHg to 87 +/- 10 mmHg (LIS) and to 88 +/- 9 mmHg (NIT) and during the night from 95 +/- 9 mmHg to 86 +/- 8 mmHg (LIS) and to 79 +/- 7 mmHg (NIT). Cumulative sodium excretion 6 hr after an acute sodium load increased to 52 +/- 39 mmol (placebo), 96 +/- 44 mmol (LIS, P < 0.05 vs. placebo), and 71 +/- 34 mmol (NIT). Glomerular filtration rate, cumulative dopamine excretion, ANP, and endothelin excretion did not differ between either treatment group. We conclude, that: (1) both drugs were similar in lowering office BP and during the day, but NIT tended to be more effective during the night; and (2) cumulative sodium excretion during LIS was significantly increased compared with placebo. There was a similar trend during NIT also. Therefore, it is possible that chronic angiotensin-converting enzyme inhibition and possibly calcium antagonists might improve the sodium-retaining state in CAH independent of differences in blood pressure, ANP, dopamine, or renal function.
authors.affiliation: Department of Internal Medicine, Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
authors.forename: G K
authors.initials: GK
authors.lastname: Schwietzer
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: G
authors.initials: G
authors.lastname: Kober
authors.forename: E
authors.initials: E
authors.lastname: Jungmann
authors.forename: D
authors.initials: D
authors.lastname: Stratmann
authors.forename: M
authors.initials: M
authors.lastname: Kaltenbach
authors.forename: W
authors.initials: W
authors.lastname: Schoeppe
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology* / Q000652:urine*; D007668:Kidney / Q000502:physiology; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016572:Cyclosporine; D009568:Nitrendipine; D003404:Creatinine; D017706:Lisinopril; D004298:Dopamine