Postnatal maturation attenuates pressure-evoked myogenic tone and stretch-induced increases in Ca²⁺in rat cerebral arteries

Abstract

Although postnatal maturation potently modulates agonist-induced cerebrovascular contractility, its effects on the mechanisms mediating cerebrovascular myogenic tone remain poorly understood. Because the regulation of calcium influx and myofilament calcium sensitivity change markedly during early postnatal life, the present study tested the general hypothesis that early postnatal maturation increases the pressure sensitivity of cerebrovascular myogenic tone via age-dependent enhancement of pressure-induced calcium mobilization and myofilament calcium sensitivity. Pressure-induced myogenic tone and changes in artery wall intracellular calcium concentrations ([Ca(2+)](i)) were measured simultaneously in endothelium-denuded, fura-2-loaded middle cerebral arteries (MCA) from pup [postnatal day 14 (P14)] and adult (6-mo-old) Sprague-Dawley rats. Increases in pressure from 20 to 80 mmHg enhanced myogenic tone in MCA from both pups and adults although the normalized magnitudes of these increases were significantly greater in pup than adult MCA. At each pressure step, vascular wall [Ca(2+)](i) was also significantly greater in pup than in adult MCA. Nifedipine significantly attenuated pressure-evoked constrictions in pup MCA and essentially eliminated all responses to pressure in the adult MCA. Both pup and adult MCA exhibited pressure-dependent increases in calcium sensitivity, as estimated by changes in the ratio of pressure-induced myogenic tone to wall [Ca(2+)](i). However, there were no differences in the magnitudes of these increases between pup and adult MCA. The results support the view that regardless of postnatal age, changes in both calcium influx and myofilament calcium sensitivity contribute to the regulation of cerebral artery myogenic tone. The greater cerebral myogenic response in P14 compared with adult MCA appears to be due to greater pressure-induced increases in [Ca(2+)](i), rather than enhanced augmentation of myofilament calcium sensitivity.

Postnatal kidney maturation regulates renal artery myogenic constriction

“…Developmental stage-dependent changes in myogenic tone have been reported in rat coronary arterioles, mouse and rat cerebral arteries, and porcine mesenteric arteries [4,7,14,15]. Together with our present findings, these studies suggest that myogenic response is maturation-dependent across species and vascular beds.…”

Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone

“…Arterial diameters were recorded with the SoftEdge Acquisition Subsystem (Ion-Optix, Milton, MA). All methods used in this study have been previously described in detail (12,13).…”

“…Once cannulated and equilibrated at 21°C, the artery segments were loaded with Fura-2 AM (Molecular Probes, Eugene, OR) for 20 min at a concentration of 1 M, as previously described (12,13). After loading, the arteries were washed with PSS, and the bath temperature was increased to 37°C.…”

“…For the colocalization analysis, coronal sections were extracted from the parent images using a masking routine to eliminate background contributions to the measurement statistics. These methods have previously been described in detail (12,13).…”

Increased myogenic responsiveness of skeletal muscle arterioles with juvenile growth

“…Evidence of such temporal changes in myogenic behavior comes mostly from studies on vessels upstream from the arterioles. For example, the myogenic responsiveness of mesenteric arteries from 10-day-old piglets is significantly less than that of arteries from 1-day-old piglets (44), and middle cerebral arteries from 6-mo-old rats exhibit weaker myogenic responses than those from 14-day-old rats (9). In contrast, there is no difference between neonatal mice (4 -8 days old) and adult mice (42-56 days old) in the intrinsic responsiveness of middle cerebral artery smooth muscle to myogenic stimuli, although the adult arteries develop less tone over a wide pressure range due to greater opposition of myogenic behavior by endothelium-derived vasodilators (17).…”