146 Pharmacological Research Communicat/ons, VoL 20, Supplement I/, 1988

ANTIHYPERTENSIVE ACTIVITY AND PREVENTION OF CARDIAC HYPERTROPHY IN SHR

AFTER LONG TERM TREATMENT WITH DRAMEDILOL

Go Ferni, M. Lombroso, M. Losa, S. Oneta, R. Rossi

ISF Laboratories for Biomedical Research, Trezzano s/N., Milan

Key Words: Antihypertensive,Vasodilator-beta blocking,Cardiac hypertrophy

Long ter~ treatments with traditional direct vasodllators i n

spontaneously hypertensive rats (SHR) produce favourable antihypertensive

effects as well as reduce the development of cardiac or cerebral lesions.

On the contrary these drugs are scarcely or not at all effective in

preventing cardiac hypertrophy. In this Work we studied the effects of

dramedilol (ISF 3382), an oral active antihyperten~ive agent, provided

with a dual pharmacological action: a strong vasodilator activity

combined with highly cardioselective beta blocking properties. The

compound was administered daily for three months to 4-month old SHR with

established hypertension, to verify the effects on blood pressure and on

cardiac hypertrophy after a long term treatment. Three groups of SHR were

given aqua fontis, dramedilol 20 mg/kg p.o., dramediiol 40 mg/kg p.o.

respectively, once a day. Final data, summarized in the table, show that

dramedilol significantly influenced blood pressure, without modlfying

heart rate, as well as it inhibited cardiac hypertrophy, which develops

in SHR (heart weights were statistically lower in higher dose than in

control animals). Histopathological examination revealed a lower

incidence of heart lesions in animals treated with 40 mg/kg of dramedilol

with respect to controls.

Treatment SBP mmHg baseline final

HR b/min baseline final

HEART mg/100g of body weight

Control 223 238 311 369 388 +3.2 +3.3 +6.4 +6.2 +lQ.3

224 213" 320 342 369 +3.7 +4.6 +8.0 +9.6 +4.3

220 2e6" 325 358 360* +5 .1 +4.9 +6.C +11.2 +5 .2

Dramedilol 20~mg/kg

Dramedilol 40 mg/kg

n=10; SBP=systol£c blood pressure; HR=heart rate; * p 0.05 (Dunnett t test) Vs control group