This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nazzaro, P. Articles by Pirrelli, A. Search for Related Content PubMed PubMed Citation Articles by Nazzaro, P. Articles by Pirrelli, A. Related Collections Lipids Cardiovascular Pharmacology Other hypertension Endothelium/vascular type/nitric oxide

(Hypertension. 1999;33:719-725.)
© 1999 American Heart Association, Inc.

Scientific Contribution

Distinct and Combined Vascular Effects of ACE Blockade and HMG-CoA Reductase Inhibition in Hypertensive Subjects

Pietro Nazzaro; Margherita Manzari; Massimo Merlo; Rita Triggiani; Annamaria Scarano; Luigi Ciancio; Anna Pirrelli

From the Department of Clinical Methodology and Medico-Surgical Technology, Division of Internal Medicine and Hypertension, Stress Research Center, Medical School of Bari, University of Bari, Italy.

Correspondence to Dr Pietro Nazzaro, Department of Clinical Methodology and Medico-Surgical Technology, Division of Internal Medicine and Hypertension, Stress Research Center, Medical School of Bari, University of Bari, Policlinico Consorziale, P.za G.Cesare,11-70124, Bari, Italy.

Abstract—Hypercholesterolemia and hypertension are frequently associated with elevated sympathetic activity. Both are independent cardiovascular risk factors and both affect endothelium-mediated vasodilation. To identify the effects of cholesterol-lowering and antihypertensive treatments on vascular reactivity and vasodilative capacity, we studied 30 hypercholesterolemic hypertensive subjects. They received placebo for 4 weeks, either enalapril or simvastatin for 14 weeks, and, finally, both medications for an additional 14 weeks. Postischemic forearm blood flow (MFBF) and minimal vascular resistance (mFVR) were used as indices of vasodilative capacity and structural vascular damage, respectively. Total (resting-stress-recovery phases) cardiovascular (blood pressure [BP] and heart rate [HR]) and regional hemodynamic (FBF and FVR) reactivity to stressful stimuli were calculated as area-under-the-curve (auc) (valuextime). Compared with baseline levels, simvastatin reduced total (TOT-C) and LDL cholesterol (LDL-C) (1.27 mmol/L, P<0.001 and 1.33 mmol/L, P<0.001, respectively). Enalapril also reduced TOT-C and LDL-C (0.6 mmol/L, P<0.001 and 0.58 mmol/L, P<0.05, respectively). MFBF was increased substantially by both treatments (P<0.001). Enalapril had a greater effect (-1.7 arbitrary units (AU), P<0.001) than simvastatin (-0.6 AU, P<0.05) on mFVR. During stress, FBF increased more with enalapril (4.4 FBFxminutes, P<0.001) than with simvastatin (1.8 FBFxminutes, P<0.01). Conversely, FVR stress response was reduced more with enalapril (9.1 FVRxminutes, P<0.001) than with simvastatin (2.9 FVRxminutes, P<0.01). During combination treatment, a significant (0.001>P<0.05) additive effect on hypercholesterolemia, structural vascular damage, BP, and FVR was shown. The findings suggest that angiotensin-converting enzyme (ACE) inhibition induces a larger reduction than HMG-CoA reductase blockade in vascular reactivity and structural damage in hypercholesterolemic hypertensive subjects.

Key Words: hypertension • hypercholesterolemia • cardiovascular reactivity • plethysmography • vascular damage

This article has been cited by other articles:

				S. Mangat, S. Agarwal, and C. Rosendorff Do Statins Lower Blood Pressure? Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 112 - 123. [Abstract] [PDF]

				E. Yamamoto, T. Yamashita, T. Tanaka, K. Kataoka, Y. Tokutomi, Z.-F. Lai, Y.-F. Dong, S. Matsuba, H. Ogawa, and S. Kim-Mitsuyama Pravastatin Enhances Beneficial Effects of Olmesartan on Vascular Injury of Salt-Sensitive Hypertensive Rats, via Pleiotropic Effects Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 556 - 563. [Abstract] [Full Text] [PDF]

				G. Nickenig Should Angiotensin II Receptor Blockers and Statins Be Combined? Circulation, August 24, 2004; 110(8): 1013 - 1020. [Full Text] [PDF]

				B. M. Singh and J. L. Mehta Interactions Between the Renin-Angiotensin System and Dyslipidemia: Relevance in the Therapy of Hypertension and Coronary Heart Disease Arch Intern Med, June 9, 2003; 163(11): 1296 - 1304. [Abstract] [Full Text] [PDF]

				M. Pelat, C. Dessy, P. Massion, J.-P. Desager, O. Feron, and J.-L. Balligand Rosuvastatin Decreases Caveolin-1 and Improves Nitric Oxide-Dependent Heart Rate and Blood Pressure Variability in Apolipoprotein E-/- Mice In Vivo Circulation, May 20, 2003; 107(19): 2480 - 2486. [Abstract] [Full Text] [PDF]

				H. Bos, R. H. Henning, P. E. de Jong, D. de Zeeuw, and G. Navis Do severe systemic sequelae of proteinuria modulate the antiproteinuric response to chronic ACE inhibition? Nephrol. Dial. Transplant., May 1, 2002; 17(5): 793 - 797. [Abstract] [Full Text] [PDF]

				K. Wilfert, K. Drischel, A. Unbehaun, H. Guski, P. B. Persson, and H. M. Stauss Vascular Response to Angiotensin II in Atherosclerosis : Role of the Baroreflex Hypertension, February 1, 2000; 35(2): 685 - 690. [Abstract] [Full Text] [PDF]

				A. Faggiotto and R. Paoletti Statins and Blockers of the Renin-Angiotensin System : Vascular Protection Beyond Their Primary Mode of Action Hypertension, October 1, 1999; 34(4): 987 - 996. [Abstract] [Full Text] [PDF]