Differential regulation of atrial contraction by P1 and P2 purinoceptors in normotensive and spontaneously hypertensive rats.

In the normotensive rat atrium, adenosine-5'-triphosphate and uridine-5'-triphosphate exert a biphasic effect consisting of an initial negative inotropic effect (NIE) followed by a subsequent positive inotropic effect (PIE). We comparatively studied these responses in normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Compared with NWRs, the NIE responses in the atria were lower and the PIE responses were higher in SHRs. The P1 purinoceptor antagonist, D 8-cyclopentyl-1,3-dipropylxanthine, partially blocked the NIE responses of both ATP and UTP and mildly enhanced the PIE responses in both NWRs and SHRs. Furthermore, the P2 purinoceptor blockers suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt induced a pronounced block of the PIE responses in both atria types. The PIE responses to ATP were inhibited more efficiently by nifedipine. These responses were depressed by ryanodine and, to a lesser extent, carbonyl cyanide 3-chlorophenylhydrazone in SHR atria compared with NWR atria. The higher responses in SHR rats suggest the existence of an augmented endoplasmic reticulum Ca(2+) store and faster mitochondrial Ca(2+) cycling in SHR atria compared with NWR atria. These data support the hypothesis that a dysfunction of purinergic neurotransmission and enhanced sympathetic activity are contributing factors in the pathogenesis of hypertension.

Alteration of purinergic neurotransmission in isolated atria of streptozotocin-induced diabetic rats.

Cardiac dysfunctions are described in diabetes. However, the role of purinergic neurotransmission in diabetes-related cardiovascular diseases is unknown. The purpose of this study was to evaluate the purinergic neurotransmission in isolated atria from streptozotocin-induced diabetic rats. The animals were grouped as control and diabetic with 30 days (D30) and 60 days (D60) after streptozotocin-induced diabetes. The isolated left and right atria were used in functional experiments. The effects of adenosine triphosphate, uridine diphosphate, and adenosine were evaluated on atrial inotropism and chronotropism. The antagonists 8-cyclopentyl-1,3-dipropylxanthine and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate were also used, as blockers of P1 and P2 receptors, respectively. A negative inotropic effect followed by a positive inotropic effect was induced by adenosine triphosphate in isolated atria. This negative inotropic effect was decreased by 25% in left atria of D30. Additionally, the apparent affinity for adenosine was diminished in left atria of D30, suggesting changes in P1 receptor function. No changes were found in the right atria of D30 stimulated by adenosine. The left atria and right atria stimulated by uridine diphosphate showed an increased inotropic effect of 92% and 17%, respectively. No changes were observed in left and right atria of D30 stimulated by uridine diphosphate. Our data showed the involvement of purinergic neurotransmission in diabetes-related cardiovascular changes.

A new strategy for direct measurement of sinus atrial conduction time by sinus node threshold determination in a rat-isolated atrium.

In this work we have searched for experimental evidence that would corroborate the idea that nodal threshold (NT) is the minimum electric field strength able to promote direct sinus node reset that, in turn, can be verified by a decrease in corrected sinus node recovery time (CSNRT). We have performed direct measurements of sinus node conduction time (SACT) and estimation of atrium sinus conduction time (ASCT). Stimulating pulses (pulse and train methods) generated a uniform electric field, with strength ranging from 1.5-fold to 5-fold the atrial threshold (AT), in the center of the perfusion chamber where isolated right atria were placed. The AT and NT were 67.4 and 192.7 mV cm(-1), respectively. The CSNRT values, obtained with stimulation strength below or above NT, were, respectively (ms; mean +/- standard error of mean) 38.1 +/- 0.42 and 25.2 +/- 0.30. In addition, we verified that NT corresponds to approximately 3-fold the AT; SACT was 1.34-fold ASCT and the overdrive suppression decreases with the increment of stimulation pulse strength. Therefore, by using a new and accurate approach for SNRT determination, we have provided additional experimental evidence for the development of alternative sinus node evaluation methods.

The effects of electrode position on the excitability of rat atria during postnatal development.

Cardiac excitability is determined by the direction of the electric field, which is defined by the positioning of electrodes. However, important morphological and physiological modifications that happen during the postnatal development of the heart may affect the cardiac threshold. In this work we have evaluated the effect of electrode positioning on the excitability threshold of isolated Wistar rat atria (left auricles) during postnatal development. This was performed by determining the parameters of strength-duration curves for stimuli (rheobase, chronaxie and normalized minimum pulse energy) of atria from rats at ages (days) 5, 15, 30, 60, 90 and 120. These parameters were determined using electric field stimulation in four different orientations (apex-base, base-apex, left-right and right-left). Atrial rheobase decreased by 1.5- to 4-fold with animal age and was altered by electric field orientation in a diversified way, whereas atrial chronaxie increased only with animal age. The minimum pulse energy decreased two- to nine-fold with ageing. This was mainly due to rheobase dependence with electric field direction. We showed that the appropriate cardiac stimulation depends on the effects of three combined factors (pulse parameters, electrode position and animal age) on the atrial tissue excitability.