title: Cilnidipine as an agent to lower blood pressure without sympathetic nervous activation as demonstrated by iodine-123 metaiodobenzylguanidine imaging in rat hearts.
abstract: BACKGROUND
  Administration of short-acting antihypertensive agents to patients with ischemic heart disease results in increased sympathetic nervous activity and is associated with worsened outcomes. Cilnidipine is an agent which blocks not only L-type calcium channels at the smooth muscle in the artery, but also N-type calcium channels at the presynaptic terminal. The goal of the present study was to determine the effect of cilnidipine on sympathetic nervous activity as on agent which blocks both L-type and N-type calcium channels at the presynaptic terminal, on sympathetic nervous activity in an experimental rat model using iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging.
  
  
  METHODS
  Fourteen-week-old Wistar-Kyoto rats were divided into 3 separate groups: CTR group (control: distilled water administered), Nif group (nifedipine administered), or Cil group (cilnidipine administered). Agents were administered via a stomach tube, followed by injection of MIBG via the femoral vein. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography just prior to administration of antihypertensive drugs and 150 minutes later. Initial imaging (Ce) and delayed imaging (Cd) were defined as the sum of density counts in the region of interest created by adjusting to myocardial edge, and were corrected for both physical decay and weight. The myocardial washout rate (WR) was defined as the percent change in the count density from the initial to delayed images.
  
  
  RESULTS
  Significant decreases in SBP were seen in the Nif group (from 132 +/- 3 mmHg to 85 +/- 5 mmHg, p < 0.0001) and the Cil group (from 128 +/- 4 mmHg to 92 +/- 7 mmHg, p = 0.0008), whereas no significant change in SBP was noted in the CTR group (from 123 +/- 5 mmHg to 127 +/- 3 mmHg). HR significantly increased in the Nif group (from 290 +/- 12/min to 378 +/- 14/min, p < 0.0001) but not in the CTR (from 278 +/- 3/min to 300 +/- 6/min) or Cil (from 291 +/- 6/min to 303 +/- 5/min) groups. WR was significantly greater in the Nif group (64.7 +/- 0.5%) when compared to the CTR (56.4 +/- 1.2%, p = 0.0031) or the Cil (55.4 +/- 2.2%, p = 0.0016) groups.
  
  
  CONCLUSIONS
  In contrast to nifedipine, administration of cilnidipine did not result in increased myocardial sympathetic nervous activation.
authors.affiliation: Department of Internal Medicine, Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Japan. takatosi@hyo-med.ac.jp
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sakaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Naruse
authors.forename: Miho
authors.initials: M
authors.lastname: Masai
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuchi
mesh_terms: D019797:3-Iodobenzylguanidine; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D004095:Dihydropyridines / Q000008:administration & dosage*; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation / Q000503:physiopathology*; D006329:Heart Conduction System / Q000000981:diagnostic imaging / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; C065927:cilnidipine; D009543:Nifedipine