Developmental changes in ovine cerebral artery composition and reactivity

Abstract

We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.

Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries

“…2). Although the ED,, concentration for NG did increase slightly with age in the common carotid, this difference is probably secondary to maturational increases in wall thickness and thus diffusion distance, which are well documented in this artery (1). Whereas SNAP releases nitric oxide spontaneously upon hydration, NG must diffuse into the smooth muscle cells where it can be biotransformed to release nitric oxide (19,20).…”

“…The initial treatment of all arteries was identical and has been described in detail previously (1). Briefly, we cleaned the arteries of adipose and connective tissue and cut them into ring segments 3 mm in length.…”

“…All arteries were denuded of vascular endothelium by mild mechanical abrasion, after which we mounted each vascular ring on paired wires between a force transducer (BG-10, Kulite Semiconductors, Ridgefield, NJ) and a post attached to a micrometer used to vary resting tension. In a Krebsbicarbonate solution containing (in mM) 122 NaCI, 25.6 NaHCO,, 5.56 dextrose, 5.17 KCI, 2.49 MgSO,, 1.60 CaCI,, 0.114 ascorbic acid, and 0.027 disodium EDTA, continuously bubbled with 95% 0, and 5% CO, and maintained at 38S°C (normal ovine core temperature), we slowly and repeatedly stretched freshly mounted arteries until optimum baseline tensions of 1 g for the common carotid and 0.5 g for the basilar arteries (1) remained stable for at least 30 min. We then contracted the arteries with an isotonic potassium Krebs solution containing 122 mM K+ and 31 mM Na+.…”

“…However, cGMP attained peak values more rapidly in adult (COM: 50 s; BAS 30 s) than in newborn (COM: 60-80 s: BAS, 4 M 0 s) segments and returned to baseline more slowly in newborn than in adult segments, suggesting that maturation accelerates cGMP turnover. Correspondingly, baseline levels of cGMP were In most arteries, vascular structure and function are immature at birth and change markedly during early postnatal life (1). In the cerebral circulation, this immaturity may be particularly important, because it may contribute to the high incidence of cerebrovascular complications observed in neonates (2,3).…”

“…In the cerebral circulation, this immaturity may be particularly important, because it may contribute to the high incidence of cerebrovascular complications observed in neonates (2,3). Among the few studies that have directly examined maturational changes in cerebral arteries, however, most have found that vasoconstrictor reactivity is generally higher in immature than in mature cerebral arteries (1,(4)(5)(6). Thus, the high incidence of neonatal cerebrovascular complications seems not to be a consequence of a deficit in the ability of cerebral arteries to respond to vasoconstrictor stimuli.…”