Development of the myogenic response in postnatal intestine: role of PKC

Abstract

Previous attempts to determine developmental changes in the vascular myogenic response have been confounded by the presence of competing vasoactive stimuli or the use of isolated vessels with markedly different baseline diameters. To circumvent these issues, small mesenteric arteries (diameter ∼150 μm) from 1- and 10-day-old piglets were studied in vitro under no-flow conditions. In situ studies demonstrated that the intravascular pressure and diameter of these vessels were similar in both age groups, allowing an effective comparison of the myogenic response not obscured by differences in basal diameter. The pressure-diameter relationship was age specific. Thus, although small mesenteric arteries from both age groups demonstrated myogenic constriction in response to stepwise increases in pressure (0 to 100 mmHg, in 20-mmHg increments), the intensity of contraction was significantly greater in vessels from 1-day-old piglets particularly within the pressure range normally experienced by these vessels in situ. Attenuation or activation of PKC with calphostin C or indolactam, respectively, substantially altered the pressure-diameter relationship in 1-, but not 10-day-old arteries; thus calphostin C essentially eliminated the contractile response to pressure elevation in younger subjects, whereas indolactam significantly increased the intensity of the myogenic response and shifted its activation point to a lower pressure range. Immunoblots carried out on protein recovered from these arteries revealed the presence of α, β, ε, ι, and λ; notably, expression of the α- and ε-isoforms substantially decreased between postnatal days 1 and 10.

WITHDRAWN: The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction

“…26 However, in some vessels, PKC inhibition does not affect the myogenic response. 81,88 This highlights the variability in individual components targeted by PKC in response to pressure across species and vascular beds. Therefore, it is imperative to confine conclusions regarding the modulation of myogenic responses by PKC to the actual vascular bed and species studied.…”

Feeding strategies and necrotizing enterocolitis

“…Whether this glucose is used directly as an energy source by the splanchnic mucosa or is used for the synthesis of glycoproteins such as mucin could not be determined. Van der Schoor's findings coincide with those of Su et al [20]. These latter investigators have shown in neonatal pig that the vascular myogenic response is substantially greater in the 1 day old than the 10 day old, leading the authors to speculate that this transition in regulation of vascular tone reflects the need to support the increasing oxidative demands of the neonatal splanchnic tissues following birth.…”

“…These latter investigators have shown in neonatal pig that the vascular myogenic response is substantially greater in the 1 day old than the 10 day old, leading the authors to speculate that this transition in regulation of vascular tone reflects the need to support the increasing oxidative demands of the neonatal splanchnic tissues following birth. Su et al further showed that protein kinase C (PKC), particularly the a-and the e-isoforms, is responsible for modulating these responses [20].…”

Mechanisms of myogenic response: Ca2+-dependent and -independent signaling

“…However, owing to poor selectivity of pharmacological inhibitors and complexity of distributional variation according to arterial types, it is difficult to identify the specific isoforms that are related with MR. Furthermore, there are reports that PKC inhibitors do not affect the MR (Su et al, 2003). Our previous studies showed that pharmacological inhibitor of PKC weakens MR in rabbit cerebral arteries, but not in rat cerebral, femoral and mesenteric arteries (Baek et al, 2010).…”