Effects of adrenoceptor blocking drugs on cardiovascular responsiveness to passive orthostasis: a placebo-controlled double-blind study.
OBJECTIVE
To compare the acute effects of the beta-blocker propranolol (CAS 525-66-6), beta + alpha1-blocker carvedilol (CAS 72956-09-3) and alpha1-blocker tamsulosin (CAS 106463-17-6) on the cardiovascular responses to passive orthostasis.


METHODS
The responses to passive orthostasis (tilt provocation at 60 degress for 8 min) were measured in normotensive healthy volunteers with finger-blood-pressure and whole-body impedance cardiography prior to drugs and three days after beginning the medications. The treatments were moderate oral doses of the beta-blocker propranolol HCl (40 mg twice daily, n = 7), (beta + alpha1-blocker carvedilol (12.5 mg once daily for two days and thereafter 25 mg daily, n = 7), alpha1-blocker tamsulosin HCl (0.4 mg once daily, n = 6), or placebo. The drugs were distributed in a randomised, double-blind fashion.


RESULTS
When measured prior to the head-up tilt test, propranolol and carvedilol had decreased supine systolic arterial pressure (SAP) more than placebo, and heart rate (HR) more than placebo and tamsulosin. Propranolol had decreased also pulse wave velocity more than placebo. The cardiac index (CI), stroke index (SI) and systemic vascular resistance index (SVRI) were not changed with any drugs. During the head-up tilt, tamsulosin decreased SAP and SVRI and augmented CI but not SI. The SVRI response curve with tamsulosin differed from that with propranolol or carvedilol. Also, tamsulosin increased HR compared to the beta-blocking drugs. The propranolol and carvedilol groups did not differ from each other in terms of any parameter.


CONCLUSIONS
Tamsulosin significantly decreases SAP in the passive head-up tilt, indicating that it is not purely uroselective alpha1-blocker. The responses with tamsulosin clearly differ from those with propranolol and carvedilol, the responses with the latter two being practically equal.
Nieminen
Tuomo
T
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere (Finland). tuomo.nieminen@iki.fi
Ylitalo
Ritva
R
Kööbi
Tiit
T
Ylitalo
Pauli
P
Kähönen
Mika
M
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D004244:Dizziness / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D013997:Time Factors
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D013449:Sulfonamides; D000077261:Carvedilol; D011433:Propranolol; D000077409:Tamsulosin