In Vitro Modulation of a Resistance Artery Diameter by the Tissue Renin-Angiotensin System of a Large Donor Artery

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Abstract
A local renin-angiotensin system (RAS) is present in the vasculature and might have an important role in the control of vascular resistance. In order to assess its functional role in the control of vasomotor tone, we investigated the effect of the RAS of a donor vessel (rat carotid artery) on the diameter of a recipient rat mesenteric resistance artery. Arteries were perfused in series in an arteriograph at a rate of 100 μL/min, under a pressure of 100 mm Hg. The two vessels were superfused in separate organ chambers to which drugs were added. Recipient artery internal diameter was measured continuously. Phenylephrine (0.1 μmol/L) was present in the organ baths throughout the experiments, ensuring a preconstriction of the recipient artery (236±4 to 174±3 μm, n=65 arterial segments from 34 rats). The angiotensin I–converting enzyme inhibitors (ACEIs) cilazapril (1 μmol/L) and captopril (10 μmol/L) inhibited phenylephrine-induced constriction by 30±12% (n=7, P<.001) and 20±8% (n=5, P<.01), respectively. Addition of cilazapril (1 μmol/L) or captopril (10 μmol/L) to the donor vessel chamber further inhibited the constriction by 8±3% (n=7, P<.01) and 31±10% (n=5, P<.05), respectively. The angiotensin II receptor (AT1) antagonist losartan (10 μmol/L) prevented, in part, the relaxation due to the ACEI. The association of losartan (10 μmol/L) with the bradykinin B2 receptor antagonist HOE 140 (1 μmol/L) totally prevented the relaxation due to the ACEI. Finally, angiotensin II was measured in the perfusate of the carotid artery and was found to be released at a rate of 11.9±2.2 pg in 60 minutes (n=8), which was significantly decreased to 1.4±0.4 pg in 60 minutes (n=4) by cilazapril (1 μmol/L). This study provides functional evidence that tissue-generated angiotensin II and bradykinin, produced locally and in upstream arteries, control the diameter of a resistance mesenteric artery.