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Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin.
1Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697-4625, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 18, 2001
Summary
Simulated microgravity in rats increased nitric oxide and vasoconstrictor prostaglandin activity in carotid arteries, causing vascular hyporesponsiveness to norepinephrine. These opposing endothelial changes impact blood vessel function during spaceflight.
Area of Science:
- Cardiovascular Physiology
- Space Medicine
- Endothelial Function
Background:
- Simulated microgravity via hindlimb unweighting (HU) in rats leads to vascular hyporesponsiveness to norepinephrine (NE).
- Endothelial nitric oxide (NO) is known to contribute to this hyporesponsiveness.
- The role of cyclooxygenase (COX) products in this vascular response remains unclear.
Purpose of the Study:
- To investigate the influence of cyclooxygenase products of arachidonic acid on vascular responsiveness in carotid arteries from rats exposed to simulated microgravity.
- To elucidate the interplay between nitric oxide and prostaglandin activity in mediating vascular responses under HU conditions.
Main Methods:
- Rats were subjected to 20 days of hindlimb unweighting (HU) to simulate microgravity.
- Isometric contraction of isolated carotid artery rings was measured.
- The effects of COX inhibitors (indomethacin, ibuprofen) and a thromboxane A(2) receptor antagonist (SQ-29548) were assessed.
- Experiments were conducted with and without endothelium, and in the presence of a nitric oxide synthase inhibitor (N(G)-L-nitro-arginine methyl ester).
Main Results:
- COX inhibitors and SQ-29548 reduced NE-induced contraction in HU vessels but not in control vessels.
- The effect of indomethacin on HU vessels was abolished by removing the endothelium.
- In endothelium-intact HU vessels with indomethacin, inhibiting nitric oxide synthase restored NE-induced contraction to control levels.
- HU induced increased endothelial nitric oxide activity and increased activity of a vasoconstrictor prostaglandin.
Conclusions:
- Hindlimb unweighting induces opposing endothelial changes in rat carotid arteries: increased nitric oxide activity causing hyporesponsiveness to norepinephrine, and increased vasoconstrictor prostaglandin activity attenuating the vasodilating effect of nitric oxide.
- These findings highlight a complex interplay of vasoactive mediators in response to simulated microgravity.
- Understanding these mechanisms is crucial for mitigating cardiovascular deconditioning during spaceflight.