Network Vascular Communication Initiated by Increases in Tissue Adenosine

Abstract

Vascular communication of vasomotor signals appears to coordinate the distribution of tissue blood flow. This study was performed to determine whether elevated tissue concentrations of adenosine or nitric oxide could induce vascular communicating signals. To test this, remote arteriolar responses were tested when drugs were applied either directly to an arteriole (∼20 μm diameter), or into the tissue in a region (with no vessels over 10 μm in diameter) that was 500 μm away from the arteriole and that bore no defined relationship to the flow path of the remote arteriole. In anesthetized hamster cheek pouch (n = 25), or cremaster muscle (n = 10), remote arteriolar responses were measured in response to nitric oxide (NO) donors (10^–5 to 10^–3 M), adenosine (10^–5 to 10^–3 M), or papaverine (10^–5 to 10^–2 M) applied for 40–120 s. Papaverine caused no remote response when applied directly while adenosine and NO donors caused similar, late-onset (10–20 s), dose-dependent, remote responses in both preparations. Remarkably however, only adenosine initiated a consistent remote arteriolar dilation when applied to the tissue site. Thus, increases in tissue adenosine may be critical for vascular communication of metabolic demands without regard to the specific blood flow path.

Downstream Exposure to Growth Factors Causes Elevated Velocity and Dilation in Arteriolar Networks

“…During exposure, the FITC was observed to flow out of the micropipette, over the selected arteriolar segment, and to wash away from the other locations of the network (that is, not recirculated from the remote to the local observation site, or vice versa). The micropipette tip size was 20–40 µm in diameter and the FITC flow stream was observed to be roughly double that in diameter (40–100 µm) at the point the pipette contents washed over the exposure site, as before [30]. …”

Initiation of remote microvascular preconditioning requires KATP channel activity

“…At 15 min after the stimulation at location B, we applied 10 Ϫ5 M SNP (n ϭ 6) or, in separate animals, 10 Ϫ5 M adenosine (n ϭ 6) to location A and examined the local vasoactive response. Submaximal concentrations were determined previously by this laboratory (41). Figure 4 shows the local responses to SNP or adenosine at location A before (control) and 15 min after RMP without and with ROS inhibition.…”

“…The physiological response of RMP can be triggered by a brief localized downstream stimulus. The region of the blood vessel that is exposed to the test agents is not more than 200 m in axial length, as defined previously using these techniques (41). Location B is a terminal arteriole that dilates in response to NO donors or adenosine, as defined previously for this network location (18).…”

Impaired retrograde transmission of vasodilatory signals via the endothelium in pre-eclampsia: a cause of reduced tissue blood flow?

“…However, evidence from studies on animal models, in which the existence of this pathway was established, has suggested several agonists may be involved. These include acetylcholine [26], l-arginine or nitric oxide (NO) [27], integrins [28] and adenosine [29]. The roles played by these agonists in vasodilatory signal conduction in man remain to be established.…”