Effects of long-term lercanidipine or hydrochlorothiazide administration on hypertension-related vascular structural changes.
OBJECTIVE
Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure.


METHODS
In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations.


RESULTS
For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p < 0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals.


CONCLUSIONS
These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon.
Grassi
Guido
G
Clinica Medica, Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Milan, Italy. guido.grassi@unimib.it
Quarti-Trevano
Fosca
F
Scopelliti
Francesco
F
Seravalle
Gino
G
Cuspidi
Cesare
C
Mancia
Giuseppe
G
D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D006984:Hypertrophy / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D006852:Hydrochlorothiazide; C060343:lercanidipine