Two in vitro techniques, the pressurized flow chamber and the wire myograph, commonly employed to study the structure and function of small arteries, were compared. Mesenteric arteries from Wistar-Kyoto (WKY) rats were studied at a transmural pressure (44 +/- 1 mmHg) at which they elicit optimum contraction in each system. Differences in morphological parameters were minor, but there was a marked difference in the vasoconstrictor response of arteries mounted in the wire myograph and pressure system. Endothelium-intact pressurized arteries were significantly more sensitive to norepinephrine and constricted to angiotensin II, whereas wire-mounted vessels did not. These differences in agonist-induced contraction remained after removal of the endothelium. Blockade of amine uptake mechanisms indicated that the difference in norepinephrine sensitivity between the systems resulted from an enhanced influence of neuronal amine uptake in wire-mounted arteries. These data demonstrate that the technique employed has important functional implications for the study of small artery responses in vitro and that the results of investigations into the pathophysiology of small arteries are dependent on the method used and must be interpreted with caution.

To examine the function of resistance-sized arteries in hypertension under in vitro conditions that approximate in Wvo conditions as much as possible, we mounted segments of second-order mesenteric resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats aged 12 to 13 weeks in a perfusion myograph and exposed them to conditions of constant flow and pressure. The endothelial integrity was validated both functionally and histologically. Vascular sensitivity to norepinephrine was examined when the hormone was applied either intraluminally or extraluminally and before and after removal of the endothelium. Both endothelium-dependent and -independent dilatation was assessed by the intraluminal application of acetylcholine and sodium nitroprusside, respectively. Sodium nitroprusside was applied to arteries after endothelium removal. Arterial responses were measured by changes in intraluminal diameter recorded with a video camera and imaging system. Vessels from SHR demonstrated depressed endothelium-dependent relaxation but similar endotheliumindependent relaxation and greater sensitivity to norepinephrine with both intraluminal and extraluminal application. Removal of the endothelium abolished the differences in sensitivity to norepinephrine between the two strains. The results demonstrate that resistance arteries from SHR when examined under in vitro perfusion display enhanced sensitivity to norepinephrine due to depressed endotheliumdependent dilatation, and the data suggest that functional modifications in the endothelium may play an important role in hypertensive vascular disease. (Hypertension. 1993;22:486-495.) KEY WORDS • endothelium • norepinephrine • acetylcholine • nitroprusside • vascular resistance • hypertension, genetic • rats, inbred SHR

To simulate in vivo conditions as closely as possible to in vitro conditions, we examined the morphological and functional characteristics of isolated human subcutaneous small arteries from 17 essential hypertensive patients and 14 normotensive control subjects using a perfusion myograph. Vessel segments were cannulated and exposed to conditions of constant flow and pressure. The ratio of media thickness to lumen diameter in arteries from hypertensive patients increased significantly. With the endothelium intact, sensitivity to extraluminally applied norepinephrine was not different, and this was not affected by inhibition of neuronal amine uptake with cocaine. After removal of the endothelium, sensitivity to norepinephrine was augmented in normotensive vessels to a greater extent than in hypertensive vessels. Endo-