The effects of sympathomimetics on the cardiovascular system of sheep.
1. Sheep hearts have been used to study the effects of beta-adrenoceptor (beta-AR) agonists in order to better understand the effects of common asthma treatment drugs on heart rate, cardiac power output and cardiac pathology. Hearts have been examined both in vivo and in vitro. 2. In whole anaesthetized sheep, isoprenaline, fenoterol and salbutamol induced dose-dependent increases in heart rate. Hypokalaemia in response to salbutamol was accentuated in hypoxia. Many of these hearts showed significant myocardial lesions. Hypoxia alone caused no significant cardiac response. 3. As expected, the beta 1-AR agonist dobutamine caused dose-dependent increases in heart performance (heart rate and cardiac power output). Both responses were blocked by metoprolol and propranolol. The beta 2-AR agonist salbutamol caused dose-dependent increases in heart rate and although cardiac output increased, cardiac power output remained unchanged as a consequence of the fall in peripheral resistance. The heart rate changes were blocked by metoprolol. Importantly, propranolol blocked both the heart rate response and the fall in peripheral resistance. 4. Isolated atrial strips showed a right shift of their dose-response curve to isoprenaline in the presence of the highly selective beta 2-AR antagonist ICI 118,551 at concentrations above 1 x 10(-8) mol/L. 5. We conclude that the sheep heart shows many pharmacological characteristics of the human heart which makes it a good pharmacological model in addition to its being amenable to many common techniques available for humans.
Pack
R J
RJ
Department of Physiology and Anatomy, Massey University, Palmerston North, New Zealand.
Alley
M R
MR
Davie
P S
PS
Kealey
A S
AS
Baxter
S
S
Allen
R
R
Dallimore
J A
JA
Lapwood
K R
KR
Crane
J
J
Burgess
C
C
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D012756:Sheep; D013566:Sympathomimetics / Q000494:pharmacology*
D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D013566:Sympathomimetics; D005280:Fenoterol; D004280:Dobutamine; C026777:ICI 118551; D007545:Isoproterenol; D000420:Albuterol