Effects of losartan and its combination with quinapril on the cardiac sympathetic nervous system and neurohormonal status in essential hypertension.
OBJECTIVE
Sympathetic nervous and renin-angiotensin systems play important roles in essential hypertension. This study was aimed at assessing the effects of losartan or its combination with quinapril on the cardiac nervous system and neurohormonal status in essential hypertension.


METHODS
Randomized, comparative study of 105 patients with mild essential hypertension, carried out at Shizuoka General Hospital. In phase 1, 40 hypertensives were allocated randomly into the losartan (50 mg) group or the quinapril (10 mg) group. In phase 2, 65 hypertensives, after 3 months 10 mg quinapril monotherapy, were allocated randomly into groups with 50 mg losartan (n = 32) or 5 mg amlodipine (n = 33) added to quinapril, and were treated for a further 3 months. All patients underwent [(123)I]metaiodobenzylguanidine (MIBG) imaging and neurohormonal measurements before and 3 months after treatment.


RESULTS
Both monotherapies significantly increased renin activity, while losartan monotherapy also increased angiotensin II (AII) concentration. In both the losartan and quinapril groups, the washout rate was significantly decreased (18.1 +/- 11.4 versus 13.9 +/- 11.0%, P < 0.0002 and 13.3 +/- 9.3 versus 12.3 +/- 9.1%, P < 00001, respectively) without changes in the heart to mediastinum ratio (H/M ratio). Both combined therapies lowered blood pressure to similar levels. A combination therapy with losartan and quinapril significantly increased the H/M ratio (1.93 +/- 0.29 and 2.02 +/- 0.29, P < 0.01) and decreased the washout rate (17.6 +/- 11.0 and 15.3 +/- 9.2%, P < 0.02) without affecting AII concentration, whereas a combination therapy with amlodipine and quinapril therapy did not affect the scintigraphic parameters with an increase in the AII concentration.


CONCLUSIONS
With a usual antihypertensive dose, both losartan and quinapril had a little suppressive effect on the cardiac sympathetic activity in essential hypertension. In contrast, the combination therapy with losartan and quinapril, which results in a higher degree of inhibition of the renin-angiotensin system, could suppress the cardiac sympathetic activity effectively.
Sakata
Kazuyuki
K
Department of Nuclear Medicine, Shizuoka General Hospital, 4-27-1 Kita-andou, Shizuoka, Japan. sakata@qf6.so-net.ne.jp
Yoshida
Hiroshi
H
Obayashi
Kazuhiko
K
Ishikawa
Joji
J
Tamekiyo
Hiromichi
H
Nawada
Ryuzo
R
Doi
Osamu
O
D019797:3-Iodobenzylguanidine / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007546:Isoquinolines / Q000627:therapeutic use*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D012083:Renin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D044005:Tetrahydroisoquinolines; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D019797:3-Iodobenzylguanidine; D012083:Renin; D019808:Losartan; D000077583:Quinapril