The early effects of chronic hypoxia on the cardiovascular system in the rat: role of nitric oxide

Abstract

Experiments were performed under Saffan anaesthesia on normoxic (N) rats and on chronically hypoxic rats exposed to 12% O 2 for 1, 3 or 7 days (1, 3 or 7CH rats): N rats routinely breathed 21% O 2 and CH rats 12% O 2 . The 1, 3 and 7CH rats showed resting hyperventilation relative to N rats, but baseline heart rate (HR) was unchanged and arterial blood pressure (ABP) was lowered. Femoral vascular conductance (FVC) was increased in 1 and 3CH rats, but not 7CH rats. When 1-7CH rats were acutely switched to breathing 21% O 2 for 5 min, ABP increased and FVC decreased, consistent with removal of a hypoxic dilator stimulus that is waning in 7CH rats. We propose that this is because the increase in haematocrit and vascular remodelling in skeletal muscle help restore the O 2 supply. The increases in FVC evoked by acute hypoxia (8% O 2 for 5 min) and by infusion for 5 min of α-calcitonin gene-related peptide (α-CGRP), which are NO-dependent, were particularly accentuated in 1CH, relative to N rats. The NO synthesis inhibitor L-NAME increased ABP, decreased HR and greatly reduced FVC, and attenuated increases in FVC evoked by acute hypoxia and α-CGRP, such that baselines and responses were similar in N and 1-7CH rats. We propose that in the first few days of chronic hypoxia there is tonic NO-dependent vasodilatation in skeletal muscle that is associated with accentuated dilator responsiveness to acute hypoxia and dilator substances that are NO -dependent.

Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries

“…It may also be due to decreased Ca 2ϩ sensitivity via hypoxia-mediated Rho kinase inactivation in SMCs (16,39). It has also been suggested that an increased NO or PG synthesis from the endothelium causes reduced contractions due to hypoxia (16,24,39,40); however, in the present study, the contractile responses were lower even in the presence of endothelial NO synthase and cyclooxygenase inhibitors. It is unlikely due to the decreased expression of agonist receptors, since a nonreceptor agonist KCl also showed reduced contractions.…”

“…To study various effects of hypoxia, humans, rabbits, and rats have been subjected to 12% O 2 for various times (hours or days) to decrease PO 2 by ϳ40% without any signs of distress or discomfort (11,17,24,35,40,43). We also exposed the rabbits to chronic/subacute hypoxia in a chamber with 12% O 2 for a maximum period of 5 days and did not see any signs of discomfort.…”

“…Moreover, acute or chronic hypoxia increased relaxations in rat and cat cerebral arteries (12,14) and in pig and rabbit coronary arteries (23,28) and also decreased blood pressure in rabbits and rats (35,40). This enhancement of vascular relaxations and the decrease in blood pressure were independent of NO or prostaglandins (PG) and were due to the enhanced activity of various K ϩ channels.…”

“…Another group of rabbits was housed in the normoxic chamber for control. The hypoxic chamber is supplied with N 2 and continuously monitored to maintain the level of O2 at 12% (35,40). After 5 days, blood was collected from the rabbit ear arteries while in the hypoxia chamber.…”

Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration

“…Such changes were suspected on the basis of the responses of the vessels to hypoxic demand. Indeed, several studies have demonstrated the influence of hypoxic stimulus on vessel diameters, which induces vasodilatation and congestion related to the liberation of many hypoxic mediators [6]. The release of these numerous substances, particularly nitric oxide (NO), induces significant vasodilatation and the discharge of inflammatory mediators, including vascular endothelial growth factor (VEGF), which is considered to be the main stimulus for the development of neovascularization.…”