C 030: DIFFERENTIAL REGULATION BY P1 AND P2 PURINOCEPTORS OF ATRIAL CONTRACTION IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

J Pharm Pharmacogn Res 2(Suppl. 1): S87, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 030: DIFFERENTIAL REGULATION BY P1 AND P2 PURINOCEPTORS OF ATRIAL CONTRACTION IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

Jurkiewicz A, Dantas da Silva Júnior E, de Magalhães Galvão K, Miranda-Ferreira R, Caricati-Neto A, Jurkiewicz NH and Quintella Dantas Rodrigues J.

Department of Pharmacology, Universidade Federal de São Paulo, Brazil.
Abstract

Introduction: It is known that ATP and UTP exert a biphasic effect in the normotensive rat atrium consisting in an initial negative inotropic effect (NIE) that is followed by a subsequent positive inotropic effect (PIE). We have comparatively studied here those responses in normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs).

Methods: Left atria (LA) of NWR and SHR animals (4-6 months) were isolated and mounted in isolated organ bath and submitted to transmural electrical stimulation (2 Hz, 5 ms and 8-12 V) to study the effect of ATP (10-3,5 M) and UTP (10-3,5 M) on atria inotropism in the absence or presence of the purinoceptors antagonists or calcium blockers. The results were analyzed by unpaired t test and one-way ANOVA.

Results: The NIE responses were lower and the PIE responses were higher in SHR, in comparison with NWRs. P1 purinoceptor antagonist DPCPX partially blocked the NIE responses to both ATP and UTP and mildly enhanced the PIE responses in both NWRs and SHRs. Furthermore, blockers of P2 purinoceptors Suramin and PPADS caused a pronounced blocked of the PIE responses in both atrial types. The PIE responses to ATP were inhibited more efficiently by nifedipine. In contrast those responses were depressed by ryanodine and CCCP to a lesser extent in SHR, compared with NWR atria. Higher responses in SHR rats suggest the existence of an augmented sarcoplasmic reticulum Ca2+ store and faster mitochondrial Ca2+ cycling in SHR, with respect to NWR atria.

Conclusion: These data add evidence to the hypothesis of a dysfunction of purinergic neurotransmission together with an enhanced sympathetic activity, as contributing factors in the pathogenesis of hypertension.