Changes in sympathetic neurotransmission and adrenergic control of cardiac contractility during 1,3-dipropyl-8-sulfophenylxanthine-induced hypertension.
We have explored the hypothesis that systemic hypertension induced by long-term treatment with the purinoceptor antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) might be associated with functional modifications of the adrenergic mechanisms of control of cardiac performance comparable to those described in other models of hypertension. Seven days continuous i.p. infusion of rats with DPSPX (30 micrograms/kg/hr) significantly increased systolic blood pressure. When sympathetic neurotransmission was evaluated via electrical field stimulation of atrial tissue, contractile responses were significantly reduced in hypertensive animals compared to controls. Similarly, contractile responses to exogenous norepinephrine were attenuated in tissue from hypertensive animals, thus suggesting that DPSPX treatment affects cardiac sympathetic neurotransmission via postjunctional rather than prejunctional changes. Inotropic responses of ventricular myocardium to both alpha- and beta-adrenoceptor stimulation were also significantly reduced in DPSPX-treated tissue. The responsiveness of atrial and ventricular myocardium to adenosine was unaffected by DPSPX treatment. The present study indicates that DPSPX-induced hypertension is associated with altered adrenergic regulation of the cardiac function that results in reduced inotropic responses of both atrial and ventricular myocardium to endogenous norepinephrine, as well as to adrenoceptor agonists applied exogenously. These alterations are comparable to those described in other models of genetic or induced hypertension, thus supporting the view that purinergic mechanisms may contribute to the onset and development of systemic hypertension.
Rubino
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A
Department of Anatomy and Developmental Biology, University College London, England.
Burnstock
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D000241:Adenosine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003864:Depression, Chemical; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D014970:Xanthines / Q000633:toxicity*
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010656:Phenylephrine; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine