Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

Abstract

Kim, Min-ho, and Norman R. Harris. Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide. Am J Physiol Heart Circ Physiol 291: H724 -H731, 2006. First published March 31, 2006 doi:10.1152/ajpheart.01215.2005.-Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 Ϯ 1.0 m) paired with venules with minimal leukocyte adherence (2.1 Ϯ 0.3 per 100-m length) was significantly larger than that of unpaired arterioles (24.5 Ϯ 0.8 m) and arterioles (23.3 Ϯ 1.3 m) paired with venules with higher leukocyte adherence (9.0 Ϯ 0.5 per 100-m length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10 Ϫ4 M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine-and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence. leukocyte adhesion; Tempol RESTING ARTERIOLAR TONE can be determined by various endogenous vasoactive substances, the release of which depends on the metabolic state of the tissue, as well as on hemodynamic factors such as shear stress and pressure. In addition, when an arteriole is closely paired with a venule, vasoactive substances released from the venule also play an important role in regulating arteriolar diameter, depending on various stimulated conditions such as an increase in venular shear rate (26), an increase in muscle stimulation (16), and an exogenous venular infusion of vasoactive substances (5, 11). Nitric oxide (NO), prostaglandins, and adenosine have been implicated as mediators of venule-induced arteriolar dilation. Anatomically, various sizes of arterioles from large to small are paired with venules within a short diffusion distance in most tissues, and this close arrangement enables venular-arteriolar diffusion of vasoactive substances.In this study, we hypothesized that endogenous adenosine induces venule-dependent dilation of closely paired arte...

Losartan and Ozagrel Reverse Retinal Arteriolar Constriction in Non‐Obese Diabetic Mice

“…Hein et al claimed that this localized flow control is critical for the modulation of retinal vascular tone due to the absence of autonomic innervation in the retinal circulation [ 8 , 19 ]. Whether this form of retinal arteriolar flow control is venule dependent, as is the case for adenosine in mesenteric tissue [ 25 ], and for arachidonic acid metabolites in stimulated cremaster tissue [ 15 ], has not been investigated.…”

In vivo visualization of nitric oxide and interactions among platelets, leukocytes, and endothelium following hemorrhagic shock and reperfusion

“…NO, prostaglandins, and adenosine have been implicated as mediators of venule-induced arteriolar dilation. Adenosine-and venule-dependent dilation of paired arterioles may be mediated by NO and inhibited by venular leukocyte adherence [27]. Activated platelets can release the potent vasoconstrictor thromboxane, and platelet adherence in venules was associated with the constriction of closely paired arterioles in a model of dextran sodium sulfate-induced inflammation [28].…”

An Animal Model of Sepsis in Appendicitis: Assessment of the Microcirculation

“…In addition, intravital microscopy has also been used to test novel prophylactic and therapeutic approaches that aim to prevent or attenuate manifestations of sepsis-associated microvascular disorders and cellular dysfunctions. In the mesentery, microcirculatory observations have focused on capillary obstruction, capillary or arteriolar density, microvessel reactivity and leukocyte-endothelial interactions in post-capillary venules (Harris, 2006;Kim & Harris, 2006;Nakagawa et al, 2006Nakagawa et al, , 2007Schimidt et al, 1997;Smalley et al, 2000;Walther et al, 2004;Woodman et al, 2000). A representative photomicrograph of rat mesenteric microcirculation is shown in Figure 3.…”

“…Microcirculatory dysfunctions, as seen in humans (De Backer & Dubois, 2001;De Backer et al, 2002;Groner et al, 1999;Trzeciak et al, 2007), have been shown to occur in most experimental models of sepsis (Baveja et al, 2002;Kamoun et al, 2005;Kim & Harris, 2006;Kubo et al, 1999;Nakagawa et al, 2006Nakagawa et al, , 2007Nakajima et al, 2001;Schimidt et al, 1997;Smalley et al, 2000;Waisman et al, 2006;Walther et al, 2004;Woodman et al, 2000). Endotoxin infusion is a widely used experimental model (Kim & Harris, 2006;Schimidt et al, 1997;Smalley et al, 2000;Nakajima et al, 2001).…”

“…Endotoxin infusion is a widely used experimental model (Kim & Harris, 2006;Schimidt et al, 1997;Smalley et al, 2000;Nakajima et al, 2001). Increased leukocyte-endothelial interactions and protein leakage in mesenteric microvessels have been shown to occur after acute endotoxemia in rats (Schimidt et al, 1997;Woodman et al, 2000) and cats (Walther et al, 2004).…”