Related Experiment Video
Updated: Jun 30, 2026
08:21
Intradermal Microdialysis: An Approach to Investigating Novel Mechanisms of Microvascular Dysfunction in Humans
Published on: July 21, 2023
Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine
Manabu Shibasaki1, David A Low, Scott L Davis
1Department of Environmental Health, Nara Women's University, Dallas, TX, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|September 20, 2008
Summary
Nitric oxide (NO) attenuates skin vasoconstriction through postsynaptic mechanisms. This finding clarifies how NO influences blood vessel responses in heat-stressed humans, impacting thermoregulation research.
Area of Science:
- Physiology
- Cardiovascular Research
- Thermoregulation
Background:
- Nitric oxide (NO) is known to inhibit cutaneous vasoconstrictor responsiveness during whole-body cooling and orthostatic stress in heat-stressed humans.
- The precise mechanism, whether presynaptic or postsynaptic, by which NO exerts this inhibitory effect on vasoconstriction remains unclear.
Purpose of the Study:
- To investigate whether nitric oxide (NO) impairs cutaneous vasoconstriction through postsynaptic mechanisms.
- To test the hypothesis that NO acts postsynaptically to reduce the vascular response to vasoconstrictor agents.
Main Methods:
- Skin blood flow was measured at two forearm sites using intradermal microdialysis.
- One site received the NO donor sodium nitroprusside, while the other received adenosine (a non-NO vasodilator).
- Increasing concentrations of norepinephrine were administered via microdialysis to assess vasoconstrictor responsiveness during continuous vasodilation.
Main Results:
- Norepinephrine administration decreased cutaneous vascular conductance at both microdialysis sites.
- The onset of vasoconstriction and the norepinephrine dose for 50% maximal response were significantly higher when NO was present (sodium nitroprusside site) compared to the adenosine site.
- This indicates that NO attenuated the vasoconstrictor response to norepinephrine.
Conclusions:
- Nitric oxide (NO) attenuates the cutaneous vasoconstrictor responsiveness to norepinephrine.
- The findings support a postsynaptic mechanism for NO's inhibitory action on vasoconstriction in human skin.
- This clarifies the role of NO in modulating vascular tone and thermoregulatory responses.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:23Antihypertensive Drugs: Vasodilators
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
01:16Antianginal Drugs: Nitrates and β-Blockers
In cardiovascular health, antianginal drugs combat angina pectoris — a condition marked by chest pain owing to diminished blood flow to the heart.
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
01:21Paracrine Signaling
Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
01:25Adrenergic Agonists: Indirect-Acting Agents
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
01:17Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...