PT  - JOURNAL ARTICLE
AU  - A Rubino
AU  - G Burnstock
TI  - Changes in sympathetic neurotransmission and adrenergic control of cardiac contractility during 1,3-dipropyl-8-sulfophenylxanthine-induced hypertension.
DP  - 1995 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 422--428
VI  - 275
IP  - 1
4099  - http://jpet.aspetjournals.org/content/275/1/422.short
4100  - http://jpet.aspetjournals.org/content/275/1/422.full
SO  - J Pharmacol Exp Ther1995 Oct 01; 275
AB  - 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.