Comparison between the cardiovascular effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and clonidine in the conscious sino-aortic denervated rat.
1. The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8-OH-DPAT and to determine whether there are any differences between the activation of central alpha 2-adrenoreceptors and 5-HT1A receptors in this respect. To this end, the effects of 8-OH-DPAT and clonidine have been assessed on blood pressure, heart rate, ECG and cardiac contractility indices in conscious sino-aortic baroreceptor denervated (SAD) rats and their sham-operated controls. 2. In both sham-operated and SAD rats, intravenous (i.v.) administration of 8-OH-DPAT (32 micrograms kg-1) and clonidine (8 micrograms kg-1) produced falls in systemic blood pressure, left ventricular systolic pressure and dP/dtmax. 3. 8-OH-DPAT produced similar bradycardia in each group of rats; in contrast, clonidine had a greater effect in the SAD animals. Increases of the PQ interval mirrored the heart-rate changes with both compounds. 4. No significant changes in end diastolic blood pressure or in the myocardial contractility indices dP/dtmax/P and Vmax were evident. 5. This study provides support for the view that i.v. 8-OH-DPAT lowers blood pressure and heart rate through a central mechanism. The effects occur independently of an intact baroreceptor reflex and are not associated with effects on myocardial contractility. 8-OH-DPAT shows close qualitative similarities to clonidine in this model.
Petty
M A
MA
Merrell Dow Research Institute, Strasbourg Research Center, France.
Kintz
J
J
Di Francesco
G F
GF
Fozard
J R
JR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D003714:Denervation; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003000:Clonidine