Impaired inotropic response to alpha 1- but not to beta-adrenoceptor stimulation in isolated hearts from spontaneously hypertensive rats.
OBJECTIVE
Hypertension in humans and experimental animals is known to be associated with an increase in left ventricular myocardial mass. The development of cardiac hypertrophy is not caused by increased blood pressure alone; the autonomic nervous system may also play an important role.


METHODS
The functional responses to the beta-adrenoceptor agonists isoprenaline, dobutamine, salbutamol and terbutaline, and the alpha 1-adrenoceptor agonists methoxamine, cirazoline and phenylephrine were studied in isolated (Langendorff) hearts from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls. The results were compared with data from radioligand binding experiments.


RESULTS
There was no significant difference in the increase of left ventricular pressure induced by all beta-adrenoceptor agonists studied in SHR and WKY rat hearts. Although there was no significant difference in the response to phenylephrine, the inotropic responses to cirazoline and methoxamine proved to be significantly weaker in hearts from SHR than in those from WKY rats. Binding experiments with 3H-prazosin revealed no differences in density or affinity for cardiac tissues from SHR and WKY rats.


CONCLUSIONS
Long-standing hypertension leads to an impaired response of the isolated heart to alpha 1-adrenoceptor stimulation, without changes in alpha 1-receptor density or affinity. It seems likely that changes in postreceptor events are responsible for the impaired inotropic response to alpha 1-adrenoceptor agonists in hearts from SHR.
Department of Pharmacotherapy, Academisch Medisch Centrum, Amsterdam, The Netherlands.
M J
MJ
Mertens
H D
HD
Batink
M
M
Pfaffendorf
P A
PA
van Zwieten
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000032:analysis; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha