Effects of a mononitrate, a beta1-blocker and a dihydropyridine calcium channel blocker on cardiovascular responsiveness to passive orthostasis: a placebo-controlled double-blind study in normotensive volunteers.
OBJECTIVE
The aim of this study was to compare the influences of antianginal drugs such as mononitrate, beta-blocker and calcium channel blocker on cardiovascular responsiveness to orthostasis.


METHODS
The responses to passive orthostasis (tilt provocation at 60 degrees for 3 min) were measured in normotensive healthy volunteers with whole-body impedance cardiography and finger blood-pressure monitoring after a single moderate oral dose of isosorbide-5-mononitrate (CAS 16051-77-7, 10 mg), the beta1-blocker bisoprolol fumarate (CAS 104344-23-2, 5 mg), the dihydropyridine calcium channel blocker nisoldipine (CAS 63675-72-9, 5 mg), and placebo in a randomised, double-blind fashion.


RESULTS
In supine position, none of the drugs altered pre-tilt arterial pressure or heart rate (HR) when compared to placebo. Nisoldipine decreased systemic vascular resistance index (SVRI) when compared to either placebo or bisoprolol, and increased the cardiac index (CI) when compared to placebo. During the passive orthostasis, the mononitrate decreased SVRI when compared to placebo or bisoprolol. The mononitrate increased HR and pulse wave velocity (PWV) when compared to the other study groups, and decreased the stroke index when compared to placebo. In the bisoprolol group, the tilt responses of diastolic arterial pressure, HR, CI, left cardiac work index, and PWV decreased significantly compared to those in the placebo group. Nisoldipine did not alter the responses to orthostasis when compared to placebo. When compared to the mononitrate, both nisoldipine and bisoprolol decreased CI response to orthostasis.


CONCLUSIONS
The mononitrate adversely affects the cardiovascular responsiveness to orthostasis. The beta-blocker reduces the responses and thus probably oxygen demand during orthostasis. The dihydropyridine calcium blocker seems to influence the responsiveness less than the mononitrate or beta-blocker.
Ylitalo
Ritva
R
Department of Pharmacological Sciences, University of Tampere Medical School, Tampere, Finland. ritva.ylitalo-heikkala@medfiles.fi
Kähönen
Mika
M
Nieminen
Tuomo
T
Kööbi
Tiit
T
Ylitalo
Pauli
P
Turjanmaa
Väinö
V
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D015737:Nisoldipine / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D016683:Supine Position / Q000502:physiology; D018667:Tilt-Table Test
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D020030:Nitric Oxide Donors; D015737:Nisoldipine; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate