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


METHODS
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).


CONCLUSIONS
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.
Tran
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Department of Clinical Pharmacology, St. George Hospital, University of New South Wales, Gray St. Kogarah, NSW, Australia.
Lowy
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A
Howes
J B
JB
Howes
L G
LG
D000109:Acetylcholine; D000368:Aged; D000704:Analysis of Variance; D000804:Angiotensin II; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000627:therapeutic use; D009638:Norepinephrine; D011725:Pyridines / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D019323:omega-N-Methylarginine; C086276:cerivastatin; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine