Effects of lercanidipine on forearm and calf vascular structural changes in hypertension

Abstract

It is still undetermined whether pharmacological regression of vascular structural changes associated with hypertension depends on the drug-induced blood pressure reduction “per se” or rather on the antihypertensive effects of the drug coupled with its additional properties (e.g., antioxidative effects, vascular selectivity, etc.). To clarify this aspect in 24 mild to moderate untreated essential hypertensives (age: 47.3 ± 0.5 years; mean arterial pressure, MAP: 115.4 ± 3.6 mmHg, mean ± SEM), with no other major cardiovascular or non-cardiovascular diseases, we measured beat-to-beat MAP (Finapres), heart rate (HR, EKG), forearm and calf blood flows (FBF, CBF, venous occlusion plethysmography) and calculated forearm and calf vascular resistance (FVR:MAP/FBF,CVR:MAP/CBF respectively). We also evaluated forearm and calf minimal vascular resistance (FVRmin and CVRmin) following 12 min of local ischaemia associated with 2 min of isometric exercise. The entire protocol was performed in the no drug condition and repeated following a 6 month treatment with lercanidipine (L, 10 mg/day per os, n = 12) of hydrochlorothiazide (H, 25 mg/day per os, n = 12) accordingly to a double blind design. L caused a significant (p < 0.01) reduction in MAP (−12.9 ± 1.1 mmHg), FVR (−12.6 ± 1.6 U) and CVR (−15.1 ± 1.7 U) without affecting HR values. These effects were coupled with a significant reduction in FVRmin (from 3.1 ± 0.3 to 2.0 ± 0.2 U, p < 0.01) and in CVRmin (from 4.6 ± 0.3 to 3.5 ± 0.3 U, p < 0.05). In contrast, for similar MAP reduction (−10.8 ± 1.4 mmHg, p < 0.01), H caused a slight decrease in FVR and CVR (−6.5 ± 1.3, −7.6 ± 1.5 U respectively) without significantly affecting FVRmin and CVRmin. These data provide evidence that for similar blood pressure reductions only drugs, such as L with additional vasoprotective properties, are capable of favouring a regression of the vascular structural changes associated with hypertension. This implies that the blood pressure reduction “per se” may be not sufficient to cause regression of vascular hypertrophy.