Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers

摘要

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 (2×20 mg/day) and ISDN (3×20 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. Day 1 to day 8 changes in heart rate and cardiac index were small but differed between ISDN and nicorandil. These differences were due to a smaller increase in HR and CI at day 8 than at day 1 with ISDN. Data on blood pressure and heart rate are in accordance with drug tolerance seen with ISDN but not with nicorandil. However, ISDN drug tolerance was not seen for the diameter of large arteries. In conclusion, with dosages used in angina, compared to nicorandil—a drug with both a potassium channel opening property and a nitratelike action—the pure nitrate ISDN showed a more pronounced decrease in systolic and diastolic blood pressure, a slight increase in heart rate, and more vasodilation of CCA. ISDN drug tolerance was shown for blood pressure and heart rate. In contrast to the well-known venous tolerance during ISDN, there was no ISDN drug tolerance for the effects on diameter of large arteries. No drug tolerance was seen with nic