The Effects of Gap Junction Modulators on the Rhythmic Contractions in Aortas Isolated from Rats Subjected with Sinoaortic Denervation

Abstract

The sinoaortic denervation (SAD) is a proceeding that interrupts the arterial baroreceptor reflex system. The hemodynamic alterations produced by SAD have been extensively studied in many mammals, including rats. There is general agreement that SAD causes a substantial increase in arterial pressure lability with no changes in the mean level of blood pressure.1-3) Therefore, SAD rats can be used to study physiological changes caused by high arterial pressure lability without sustained hypertension. There are few studies analyzing physiological aspects of isolated vessels of SAD rats.Smooth muscle is frequently classified by the manner in which it responds to excitatory stimulation. Therefore, tonic smooth muscle such as that often found in vasculature, airways, gastrointestinal and urogenital systems responds to contractile agonists by producing a simple steady contraction. In contrast, many previous studies have shown that some isolated smooth muscle preparations generate rhythmic contractions (RCs), mainly arterial beds isolated from hypertensive animals. [4][5][6][7][8] Gap junctions are membrane-localized channels which allow intercellular movement of small molecules (relative molecular mass Յ1000), thereby greatly facilitating intercellular communication and coordination of cellular activities.9,10) Gap junctions are blocked by heptanol 10,11) and they can be activated or recruited by tetraethylammonium. 12,13) Gap junctions play a significant role in establishing smooth muscle cell communication in the uterus, which display intense RCs. 14,15) This oscillatory behavior in the uterus is straight associated with an increase in gap junction complex formation between smooth muscle cells.15) Furthermore, inhibitors of gap junctions such as heptanol 16,17) reduce the RCs in the uterus. Isolated rat aortas normally present tonic and stable contractions when stimulated to contract. However, SAD rat aortas present RCs, which are characterized by cycles of fluctuations in tension. 18) In the present study, we also demonstrated an oscillatory behavior in aortas isolated from SAD rats. Additionally, the effect of heptanol and tetraethylammonium (TEA) was investigated in order to explore the role of gap junctional communication on the RCs and supply a pharmacological consideration of the participation of these cellular coupling on vascular reactivity and RCs in aortas from rats with arterial pressure lability evoked by SAD. MATERIALS AND METHODSSinoaortic Denervation All the procedures were carried out in accordance with the Ethical Animal Committee, Ribeirão Preto Campus, University of São Paulo, Brazil. Male Wistar rats (180-210 g) were used throughout the study. Bilateral sinoaortic denervation was performed according to the method reported by Krieger.19) Briefly, the rats were anesthetized with ketamine (50 mg/kg, intraperitoneally (i.p.)) and xylazine (5 mg/kg, i.p.), and suitably fixed in a supine position. An extensive (3-4 cm) middle incision was made into the neck, and the bilateral sternohyoid muscle was rese...

Role of connexin 43 in vascular hyperpermeability and relationship to Rock1-MLC20pathway in septic rats

“…Cx37, Cx40, Cx43, Cx45, and Cx46 are the main Cxs in the cardiovascular system (23,31). It has been shown that the functional abnormalities of gap junctions are related to several cardiovascular diseases, such as atherosclerosis, hypertension, and arrhythmias (44,37). Angelillo-Scherrer et al (5a) reported that deletion of Cx37 in mice shortened the bleeding time and increased thrombus propensity, thus providing a mechanism by which Cx37 limits thrombus propensity by downregulating platelet reactivity.…”