title: Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients.
abstract: OBJECTIVE
  To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg).
  
  
  METHODS
  After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges.
  
  
  RESULTS
  Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05).
  
  
  CONCLUSIONS
  The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.
authors.affiliation: Hôpital du Sacré-Coeur and Campus Hôtel-Dieu, Faculty of Medicine, Université de Montréal, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: de Champlain
authors.forename: M
authors.initials: M
authors.lastname: Karas
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.forename: P
authors.initials: P
authors.lastname: Cartier
authors.forename: R
authors.initials: R
authors.lastname: Wistaff
authors.forename: C B
authors.initials: CB
authors.lastname: Toal
authors.forename: R
authors.initials: R
authors.lastname: Nadeau
authors.forename: P
authors.initials: P
authors.lastname: Larochelle
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood*; D016037:Single-Blind Method; D013599:Systole; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D017311:Amlodipine; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine