Effects of cerivastatin on forearm vascular responses, blood pressure responsiveness and ambulatory blood pressure in type 2 diabetic men

Abstract

Objective: The objective of the study was to investigate the effects of cerivastatin therapy on forearm endothelial dependent acetylcholine (ACH) and independent (nitroprusside) vasodilator responses, blood pressure (BP) responses to intravenous infusions of angiotensin II (AII) and noradrenaline (NA) and on 24-h ambulatory BP recordings in type 2 diabetic men.

Design: Eleven type 2 diabetic men aged 59 +/- 9 years with total cholesterol levels of 5.0 +/- 1.26 mmol/l, triglycerides of 2.23 mmol/l and high-density lipoprotein cholesterol levels of 1.24 mmol/l completed a double-blind, randomized, crossover trial comparing 8 weeks of cerivastatin therapy (800 microg of nocte) with placebo. Forearm vascular resistance (FVR) responses to intrabrachial-arterial infusions of ACH (3-24 microg/min), nitroprusside (2-16 microg/min), the nitric oxide(NO) synthase inhibitor l-nitro-mono-methyl arginine (l-nmma) (8 micromol/min), ACH during l-NMMA infusion and BP responses to intravenous infusions of AII (12.5-50 ng/min) and NA (20-400 ng/min) were measured at the end of each treatment period. Twenty-four-hour ambulatory BP recordings were also performed.

Results: FVR responses to ACH during l-NMMA infusion were significantly (p = 0.026) greater during cerivastatin than during placebo therapy. In contrast, FVR responses to ACH in the absence of NO synthase inhibition did not differ significantly between cerivastatin and placebo therapies (p = 0.81). FVR increased by 31.4 +/- 57.3% in response to l-NMMA infusion during cerivastatin therapy compared with 6.1 +/- 41.2% during placebo therapy (p = 0.20). FVR responses to nitroprusside did not differ between cerivastatin and placebo therapies (p = 0.28), nor did BP responses to AII (systolic BP, p = 0.99; diastolic BP, p = 0.98) or NA (systolic BP, p = 0.21; diastolic BP, p = 0.48). Mean 24-h BP was similar during cerivastatin (123 +/- 10 or 70 +/- 7 mmHg) and placebo therapies (129 +/- 11 or 74 +/- 7 mmHg) (systolic BP, p = 0.26; diastolic BP, p = 0.41).

Conclusion: Cerivastatin increases FVR responses to ACH in type 2 diabetic men with mild dyslipidaemia but only following NO synthase inhibition. This may indicate an improvement in endothelium-derived hyperpolarizing factor-mediated responses.