Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers.
Nicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18-32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscular femoral (FA) and brachial (BA) arteries were investigated. The effects on systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and venous hemodynamics were also assessed. In addition, the subacute effects after 8 days of treatment with N (2 x 20 mg/day) and ISDN (3 x 20 mg/day) on these parameters were evaluated. After a 20 mg single oral dose, blood pressure decreased significantly more with ISDN (SBP: 6%; DBP: 14%) than with N (SBP: 2%; DBP: 6%), but after 8 days this decrease in blood pressure was not statistically different between ISDN and N. The diameter of CCA increased more with ISDN (11%) than N (5%) acutely as well as subacutely (ISDN: 12%; N: 9%). Heart rate increased only with ISDN (7% acutely, 3% subacutely). No differences between ISDN and nicorandil were found for acute and subacute effects on SVRI, venous hemodynamics, diameter of muscular arteries (FA, BA), and the distensibility and compliance of elastic (CCA) and muscular (FA, BA) arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Kool
M J
MJ
Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Spek
J J
JJ
Struyker Boudier
H A
HA
Hoeks
A P
AP
Reneman
R S
RS
van Herwaarden
R H
RH
Van Bortel
L M
LM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D003187:Compliance / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D015150:Echocardiography, Doppler; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D012044:Regression Analysis; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D015415:Biomarkers; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D007548:Isosorbide Dinitrate