Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms

Abstract

Pearce. Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms. Am J Physiol Regul Integr Comp Physiol 284: R734-R741, 2003. First published December 5, 2002 10.1152/ajpregu.00510.2002In light of previous observations that the range of arterial pressures over which cerebral blood flow is autoregulated differs dramatically in neonates and adults, the present experiments explored the hypothesis that pressure-induced intrinsic arterial tone is regulated differently in neonatal and adult cerebral arteries. In cannulated and pressurized endothelium-intact mouse cerebral arteries Ͻ150 m in diameter, active intrinsic tone was evident at intraluminal pressures as low as 10 mmHg in neonatal arteries, but only at pressures of 60 mmHg or greater in adult arteries. Administration of 10 M indomethacin produced no significant effect on tone at any pressure in either neonatal or adult arteries, but subsequent addition of 100 M nitroarginine methyl ester (NAME) significantly vasoconstricted both neonatal and adult arteries at all pressures. Conversely, administration of 100 M NAME alone significantly vasoconstricted adult arteries only, and subsequent addition of 10 M indomethacin produced a significant additional vasoconstriction in adult arteries only, indicating an important interaction between the nitric oxide synthase and cyclooxygenase pathways, at least in adult arteries. In the presence of both indomethacin and NAME, intrinsic tone was significantly greater in neonatal than adult arteries, but when the endothelium was removed, tone was similar in neonatal and adult arteries at all pressures. Together, these results suggest that pressure-induced myogenic tone is regulated similarly in neonatal and adult mouse cerebral arteries but that the contribution of endothelial vasoactive factors to intrinsic tone is highly age dependent. neonatal mouse; myogenic tone; pressure; cerebral artery NOT LONG AFTER the establishment of the nitrous oxide method for measurement of human cerebral blood flow in the late 1950s, it was widely recognized that cerebral perfusion was regulated independent of arterial pressure between pressures of Ϸ60 and Ϸ160 mmHg (22,25,37). This pattern of regulation, termed "cerebral autoregulation," has since been the focus of more than 2,600 studies that together indicate involvement of multiple different mechanisms in this response.Most important among these are the myogenic mechanisms that transduce changes in intraluminal hydraulic pressure and/or vascular wall stresses into changes in vascular smooth muscle contractility (10, 16). Release of vasoactive substances from the vascular endothelium in response to changes in shear stress also undoubtedly contributes to cerebrovascular autoregulatory adjustments (13). In addition, autonomic neurovascular mechanisms can potently influence the arterial pressure range over which cerebral autoregulation is effective (6).Owing to the central role of cerebral autoregulation for maintenance of cerebrovascular homeostasis, insults tha...

Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries

“…Data from the present study suggest that when compared with adult rat cerebral arteries, newborn porcine cerebral arteries exhibit a different pattern of responses to intravascular pressure. One principal difference is that newborn porcine cerebral arteries exhibit significant myogenic tone (ϳ19% of passive diameter) at 10 mmHg, consistent with previous findings in neonatal mouse middle cerebral arteries and newborn porcine mesenteric arteries (16,46). Enhanced sensitivity to stretch has also been reported in the newborn when compared with adult guinea pig large pulmonary arteries (6).…”

“…A functional myogenic response is known to be present at the newborn stage of development and appears to involve the activation of voltagedependent Ca 2ϩ channels (17). Similarly, in newborn rodent cerebral arteries, a step increase in intravascular pressure elevates [Ca 2ϩ ] i and induces constriction (16,17,34). Nisoldipine, an L-type Ca 2ϩ channel blocker, reduces arterial wall [Ca 2ϩ ] i and dilates pressurized newborn rat cerebral arteries (17), suggesting that the pressure-induced [Ca 2ϩ ] i elevation occurs due to voltage-dependent Ca 2ϩ channel activation.…”

Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice

“…In the present study, mouse MCAs did not develop myogenic tone in response to pressure and flow. In the absence of luminal flow, previous studies have found that mouse MCAs developed myogenic tone in response to pressure (2,12,13). For example, at 80 mmHg, Ͻ10% tone was observed in MCAs Fig.…”

Changes in Coronary Resistance Related to the Stages of the Female Life Cycle

“…18,22,23 The cerebral arterial tone is regulated differently in neonates and adults. Cerebral arterial dilatation in newborn piglets is entirely prostanoid dependent, whereas it requires both NO and prostanoids in juveniles.…”