Impaired flow-dependent dilatation in distal mesenteric arteries from the spontaneously hypertensive rat

Abstract

1. The aim of the study was to examine the hypothesis that flow-dependent dilatation is impaired in distal mesenteric arteries from adult spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rat (WKY) controls and to assess the role of nitric oxide (NO). 2. Arterial segments were cannulated, pressurized to 80 mmHg and allowed to develop spontaneous myogenic tone. Flow was increased incrementally in vessels from both strains and responses were also assessed before and after incubation with the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Responses to flow in control vessels were also assessed before and after intraluminal perfusion with antibody-complement to disrupt the endothelium. 3. At a flow rate of 5 microliter min-1, arteries from the WKY dilated significantly (22 +/- 5%, P < 0.01, n = 29) compared with the diameter at zero flow, whereas arteries from the SHR did not (4 +/- 4%, n.s., n = 16). Incubation with L-NAME had no inhibitory effect on the responses to flow in either rat strain. In control arteries, antibody-complement treatment abolished the dilatation in response to both flow and acetylcholine (ACh, 1 microM). 4. We conclude that flow-dependent dilatation is impaired in distal mesenteric arteries from adult SHR compared with WKY controls. Furthermore, flow-dependent dilatation is endothelium dependent, but L-NAME insensitive, thus excluding the NO pathway in this abnormality. Impaired flow-dependent dilatation may contribute to the increased peripheral resistance in hypertension.

Figure 1. Effect of intraluminal flow on the diameter of distal mesenteric arteries from the SHR compared with WKY controls

Flow-diameter relation of distal mesenteric arteries from SHR (□) and WKY controls (○). * P < 0.01 lumen diameter with intraluminal flow compared with zero flow; † P < 0.05 lumen diameter of SHR vs. WKY (n = 8 in each group).

Figure 2. Representative recordings of the response to flow in a distal mesenteric artery from the SHR and WKY control

Proximal pressure, distal pressure and diameter recording as intraluminal flow is increased incrementally to 20 μl min⁻¹, followed by dilatation in response to ACh (1 μM), in a distal mesenteric artery from the SHR (A) and WKY control (B).

Figure 3. Reproducibility of flow-dependent dilatation

Time control experiments using distal mesenteric arteries from WKY, demonstrating reproducibility of flow-dependent dilatation when the maximum flow rate is 5 μl min⁻¹ (n = 6). ○, first response; □, second response.

Figure 4. Effect of L-NAME on the response to intraluminal flow in distal mesenteric arteries from the SHR and WKY

Flow-diameter relation before (○) and after (□) 30 min incubation in L-NAME (10⁻⁴ M). A, SHR (n = 8); B, WKY (n = 7). * P < 0.05, L-NAME vs. control.

Figure 5. Effect of endothelial disruption on flow-dependent dilatation

Flow-diameter relation in distal mesenteric arteries from the WKY rat before (○) and after (□) endothelial disruption by intraluminal perfusion with M199-5 % BSA containing anti-human factor VIII-related antigen antibody (13.4 μg ml⁻¹) and 4 % guinea-pig complement (n = 4). * P < 0.05 endothelial disruption vs. control.