Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature

Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT(1)Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT(1)R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT(1)R isotypes: AT(1)R(a) and AT(1)R(b). We previously demonstrated that AT(1)R(b) is expressed at much higher levels compared with AT(1)R(a) in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT(1)R(a) is unnecessary for this function. Here, we found that AT(1)R(a) and AT(1)R(b) are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT(1)R(b) and total AT(1)R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT(1)R ligand angiotensin II (ANG II). We conclude that 1) AT(1)Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT(1)R(b) and total AT(1)R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments. NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT(1)R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT(1)R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.