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Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction
Anastasia Z Kalea1, Patrick D Harris, Dorothy J Klimis-Zacas
1Department of Food Science and Human Nutrition, College of Natural Sciences, Forestry and Agriculture, University of Maine, Orono, ME 04469, USA.
Abstract:
We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P=.001). Thus, dietary Mn at levels of 45-50 ppm affects the contractile machinery by reducing maximal vessel contraction to an alpha(1) adrenergic agonist. The observed pD(2) was significantly greater in the MnD group compared with the MnA and MnS animals (P=.001). Thus, restriction of dietary Mn affects vascular sensitivity to the alpha(1) adrenergic receptor. Our results demonstrate for the first time that dietary Mn influences the receptor signaling pathways and contractile machinery of vascular smooth muscle cells in response to an alpha(1) adrenergic receptor.
Insights
Dietary manganese (Mn) impacts rat aorta function. High manganese levels reduced maximal contraction force, while deficiency increased vascular sensitivity to alpha(1) adrenergic receptors, affecting smooth muscle cells.
Area of Science:
- Cardiovascular Physiology
- Nutritional Biochemistry
- Vascular Pharmacology
Background:
- Dietary manganese (Mn) is essential for various physiological processes.
- The specific effects of dietary manganese on vascular smooth muscle contractility are not fully understood.
Purpose of the Study:
- To investigate the impact of varying dietary manganese levels on the contractile machinery of rat thoracic aortas.
- To determine how manganese influences vascular smooth muscle cell response to alpha(1) adrenergic receptor stimulation.
Main Methods:
- Weanling male Sprague-Dawley rats were fed manganese-deficient, adequate, or supplemented diets for 15 weeks.
- Aortic rings were contracted with L-phenylephrine (alpha(1) adrenergic agonist) and relaxed with acetylcholine.
- Maximal contraction force (Fmax) and sensitivity (pD2) to L-phenylephrine were measured.
Main Results:
- Manganese-supplemented diet (45-50 ppm) resulted in lower maximal contraction force (Fmax) compared to deficient and adequate groups.
- Manganese deficiency significantly increased vascular sensitivity (pD2) to L-phenylephrine.
- Hepatic manganese content indicated successful dietary manipulation and affected animal growth rates.
Conclusions:
- Dietary manganese levels significantly influence the contractile machinery of vascular smooth muscle.
- High dietary manganese reduces maximal contractile responses to alpha(1) adrenergic agonists.
- Manganese deficiency enhances vascular sensitivity to alpha(1) adrenergic receptor stimulation, impacting signaling pathways.
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