The mechanisms of action involved in the vasorelaxant effect of gallic acid (GA) were examined in the isolated rat thoracic aorta. GA exerted a relaxant effect in the highest concentrations (0.4-10mM) in both endothelium-intact and endothelium-denuded aortic rings. Pre-incubation with L-NAME, ODQ, calmidazolium, TEA, 4-aminopyridine, and barium chloride significantly reduced the pEC50 values. Moreover, this effect was not modified by indomethacin, wortmannin, PP2, glibenclamide, or paxillin. Pre-incubation of GA (1, 3, and 10mM) in a Ca(2+)-free Krebs solution attenuated CaCl2-induced contractions and blocked BAY K8644-induced vascular contractions, but it did not inhibit a contraction induced by the release of Ca(2+) from the sarcoplasmatic reticulum stores. In addition, a Western blot analysis showed that GA induces phosphorylation of eNOS in rat thoracic aorta. These results suggest that GA induces relaxation in rat aortic rings through an endothelium-dependent pathway, resulting in eNOS phosphorylation and opening potassium channels. Additionally, the relaxant effect by an endothelium-independent pathway involves the blockade of the Ca(2+) influx via L-type Ca(2+) channels.

The aim of this study was to evaluate and compare the effects of early and physiological menopause on cardiac autonomic parameters in aged female rats. To this end, female Wistar rats (22 and 82 weeks old, N=96) were divided into 4 groups: Young Sham-operated Rats, Aged Sham-operated Rats, Young Ovariectomised (OVX) Rats, and Aged OVX Rats. Young Sham-operated and OVX rats were used as controls. The cardiac autonomic parameters were investigated using different approaches: 1) pharmacological evaluation of the autonomic tonus with methylatropine and propranolol; 2) isolated cardiac contractility with β-adrenergic agonists; and 3) quantification of the mRNA and protein level expression of cardiac β-adrenergic receptors. Among the groups of aged female rats, both the Sham-operated and OVX rats showed higher basal mean arterial pressure and heart rate (HR) values compared to their respective young counterparts. The aged groups also showed a predominance of the sympathetic autonomic component in the determination of HR, whereas the young rats showed a vagal predominance. An assessment of cardiac contractility showed that aged Sham-operated and OVX rats had lower contractile responses following the administration of dobutamine compared to their respective young counterparts. In addition, the aged groups showed higher mRNA and protein expression levels of the β1-adrenergic receptors. In conclusion, our results show that haemodynamic alterations and impairment of the autonomic parameters were similar between the groups of rats subjected to early and physiological menopause. Moreover, these results seem to be due to the ageing process and not ovarian hormone deprivation.

1. Male DOCA-salt rats exhibit vasoconstriction upon ET(B) activation. Because hypertension is less severe in female than male DOCA rats, we hypothesized that female DOCA rats would display attenuated ET(B) vasoconstrictor responses. 2. Uninephrectomized Wistar rats received DOCA and drinking water containing NaCl/KCl. Control rats received vehicle and tap water. Systolic blood pressure was higher in male vs female DOCA rats. Responses to endothelin-1 (ET-1), IRL-1620, an ET(B) agonist, and acetylcholine were evaluated in isolated aortas and in vivo in the mesenteric microcirculation. 3. Endothelium-denuded aortas from male, but not female, DOCA rats displayed increased sensitivity to ET-1. IRL-1620 contracted aortas from male DOCA rats, but not control or female DOCA aortas. Noradrenaline-constricted and endothelium-intact aortas from male, but not female, DOCA rats displayed increased relaxation to IRL-1620 compared to control aortas. 4. In vivo, increased vasoconstriction to ET-1 was observed in male and female DOCA rats. IRL-1620 induced vasodilation in control rats, but vasoconstriction in male DOCA rats. There were minimal changes in diameter in vessels from female DOCA rats. 5. The initial fall in blood pressure induced by ET-1 and IRL-1620 was attenuated in male DOCA rats. Bosentan, a mixed ET(A)/ET(B) receptor antagonist, lowered blood pressure in male and female DOCA rats, but a greater and marked decrease occurred in the male DOCA group. 6. The gender-related differences in ET-1/ET(B)-mediated effects both in the vasculature and blood pressure suggest that sex-related functional up-regulation of ET(B) receptors may play a role in the more severe hypertension in male DOCA hypertensive rats.

Abstract-We have tested the hypothesis that increased gap junctional communication contributes to the augmented endothelium-dependent vasodilation in pregnancy. Contractile force and connexin43 expression were measured in aortic rings from nonpregnant and pregnant rats. Norepinephrine-constricted aortas from pregnant rats were more sensitive to acetylcholine, but not to sodium nitroprusside, compared with those from nonpregnant rats. Vessels from pregnant rats, constricted either with 45 mmol/L KCl or with norepinephrineϩ10 Ϫ4 mol/L N G -monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, also exhibited greater relaxation to acetylcholine. Heptanol, an uncoupler of gap junctional communication, inhibited acetylcholine responses in norepinephrine-constricted aortas from nonpregnant rats but greatly impaired acetylcholine relaxation in aortas from pregnant rats. Heptanol also inhibited in both groups acetylcholine responses in vessels constricted with KCl, only minimally affected acetylcholine relaxation in arteries constricted with norepinephrineϩL-NMMA, and did not change sodium nitroprusside-induced relaxation. Tetraethylammonium chloride induced greater contractions in control aortas compared with aortas from pregnant rats. Increased connexin43 mRNA levels were found in the uterus and in the mesenteric, uterine, and thoracic aortic arteries, but not in the heart and brain, from pregnant rats. These results suggest that increased gap junctional communication, possibly due to increased gap junction protein expression, may facilitate the effects of endothelium-derived relaxing factors, contributing to the augmented endothelium-dependent relaxation in arteries from pregnant rats. Key Words: preeclampsia Ⅲ rats Ⅲ gap junctions Ⅲ nitric oxide Ⅲ endothelium-derived factor P regnancy is associated with a decrease in systemic vascular resistance, which maintains or reduces maternal blood pressure despite the increase in plasma volume and cardiac output. 1 Pregnancy in women and in other mammals, such as the rat, is also characterized by a blunted pressor response 2,3 and decreased vascular reactivity 4,5 to a series of vasoconstrictors. The mechanism(s) responsible for these cardiovascular changes in pregnancy is not fully understood but has been under intense investigation, particularly because its malfunction may have a role in preeclampsia. 6 Because blunted constrictor responses in arteries from pregnant animals are observed in vitro 4,5 and no changes in receptor number or affinity seem to occur, 2,7 it has been suggested that a general mechanism, occurring within the blood vessel wall, is involved. Enhanced endothelium-dependent vasodilation, which may contribute to the attenuated vasoconstriction during pregnancy, has been systematically shown in vessels from pregnant animals, including the uterine, mesenteric, thoracic, and abdominal aortic arteries. 8 -11 Nitric oxide (NO), but not prostaglandins, is considered to contribute substantially to the increased endothelium-dependent relaxation in...