Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) ( n = 6), habitat control (HC) ( n = 6), and vivarium control (VC) ( n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis. The results demonstrate that vasoconstriction elicited through a voltage-gated Ca²⁺ mechanism (30–80 mM KCl) and thromboxane A₂ receptors (10⁻⁸ − 3 × 10⁻⁵ M U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase activity (1 μM Y27632) abolished group differences in U46619-evoked contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10 μM, 2 μM U46619 preconstriction) was virtually absent in cerebral arteries from SF mice. The pressure-diameter relation was lower in arteries from SF mice relative to that in HC mice, which was not related to differences in the extracellular matrix protein elastin or collagen content or the elastin/collagen ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross-sectional area of unpressurized basilar arteries were not different among groups. These results suggest that the microgravity-induced attenuation of both vasoconstrictor and vasodilator properties may limit the range of vascular control of cerebral perfusion or impair the distribution of brain blood flow during periods of stress.

Functional remodelling takes place permanently in the circulatory system. Whether this process also affects the anti-contractile effect of the endothelium during vasoconstrictor action is unknown. Therefore, the hypothesis was tested that the impact of the anti-contractile effect of the endothelium on agonist-induced contractions changes during early postnatal development. We studied isometric contractions in saphenous arteries of young (1–2 weeks) and adult (2–3 months) rats. Real-time PCR and western blot were performed to evaluate the levels of mRNA expression and protein phosphorylation, respectively. In young but not in adult rats, methoxamine-induced contractions of endothelium-intact vessels exhibited a lower sensitivity compared with endothelium-denuded vessels. The endothelial influence on methoxamine-induced contractions in arteries of young rats was completely blocked by inhibition of endothelial NO-synthase (eNOS) and guanylate cyclase. NO-donor-induced vessel relaxations were not different in young and adult rats. The expression level of eNOS mRNA was prominently higher in arteries from young compared with adult rats. eNOS inhibition alone induced tonic contractions of endothelium-intact arteries from young but not from adult animals that were associated with corresponding changes in phosphorylation of the myosin regulatory light chains, the regulatory subunit of smooth muscle cell myosin light chain phosphatase, and vasodilator-stimulated phosphoprotein, the latter two being considered to be good markers of NO/sGC/PKG pathway activity. We demonstrated that agonist-induced contractions in arteries of young rats are attenuated by the endothelium possessing an active NO-pathway. The active NO-pathway is due to a constitutive eNOS activity that disappears with age.

Nitric oxide (NO) produced in the wall of blood vessels is necessary for the regulation of vascular tone to ensure an adequate blood supply of organs and tissues. In this review, we present evidence that the functioning of endothelial NO-synthase (eNOS) changes considerably during postnatal maturation. Alterations in NO-ergic vasoregulation in early ontogeny vary between vascular beds and correlate with the functional reorganization of a particular organ. Importantly, the anticontractile effect of NO can be an important mechanism responsible for the protectively low blood pressure in the immature circulatory system. The activity of eNOS is regulated by a number of hormones, including thyroid hormones which are key regulators of the perinatal developmental processes. Maternal thyroid hormone deficiency suppresses the anticontractile effect of NO at perinatal age. Such alterations disturb perinatal cardiovascular homeostasis and lead to delayed occurring cardiovascular pathologies in adulthood. The newly discovered role of thyroid hormones may have broad implications in cardiovascular medicine, considering the extremely high prevalence of maternal hypothyroidism in human society.