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Age-related changes in vascular responses
J Marín1, M A Rodríguez-Martínez
1Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo 4, 28029, Madrid, Spain. jesus.marin@uam.es
Insights
Aging impairs blood vessel function, increasing cardiovascular disease risk. Key changes include reduced nitric oxide, altered calcium handling, and impaired sodium pump activity, impacting vascular tone and drug responses in older adults.
Area of Science:
- Cardiovascular Physiology
- Gerontology
- Vascular Biology
Background:
- Aging significantly alters blood vessel structure and function, elevating the risk of cardiovascular diseases like hypertension and heart failure.
- These age-related vascular changes are exacerbated by hypertension, leading to increased morbidity and mortality.
- Endothelial cell dysfunction in aging reduces nitric oxide production, impairing endothelium-dependent relaxations.
Purpose of the Study:
- To investigate the specific functional and structural changes in blood vessels associated with aging.
- To understand how aging affects vascular tone regulation, including both endothelium-dependent and independent responses.
- To explore alterations in vascular calcium (Ca2+) homeostasis and sodium (Na+) pump activity during the aging process.
Main Methods:
- Analysis of vascular tone regulation, comparing age-related changes in endothelium-dependent and independent relaxations.
- Assessment of contractile responses to various agonists (e.g., noradrenaline, endothelin, histamine) in aged versus younger vessels.
- Evaluation of vascular extracellular Ca2+ dependence and Na+ pump activity, including responses to ouabain and the role of endothelial factors.
Main Results:
- Aging reduces endothelium-dependent relaxations due to decreased nitric oxide synthesis/release, while endothelium-independent relaxations are largely preserved.
- Contractile responses to most agents remain unchanged, except for reduced sensitivity to noradrenaline and endothelin.
- Vascular Ca2+ homeostasis is altered, increasing extracellular Ca2+ dependence and sensitivity to Ca2+ antagonists in the elderly; Na+ pump activity is reduced, with a loss of inhibitory endothelial factors and gain of contracting factors.
Conclusions:
- Aging profoundly impacts vascular function, characterized by impaired endothelial function, altered calcium handling, and reduced sodium pump activity.
- These age-related vascular changes contribute to increased cardiovascular disease incidence and altered responses to vasoactive agents and medications.
- Understanding these mechanisms is crucial for managing cardiovascular health and optimizing therapeutic strategies in the aging population.
Abstract:
Aging causes changes in the structure and function of the vessels that leads to an increase in the incidence of certain cardiovascular diseases, such as hypertension, coronary artery disease, heart failure, and postural hypotension with enhancement of both morbidity and mortality. When aging is associated with hypertension, these changes are increased. Aging alters endothelial cells, and so the vascular tone regulation, reducing the endothelium-dependent relaxations, probably by a decrease in endothelial synthesis or release of nitric oxide. In addition, endothelium-independent relaxations are essentially unaltered, those elicited by beta-adrenoceptor agonists being usually reduced. Aging scarcely modifies the contractions induced by different agents, such as 5-hydroxytryptamine, histamine, high potassium, and angiotensin, whereas reduces those elicited by noradrenaline or endothelin. Vascular Ca(2+) homeostasis appears to be altered in aging. The extracellular Ca(2+) dependence of contractile responses elicited by agonists is enhanced, which explains the increased sensitivity to Ca(2+) antagonists in elderly. Finally, Na(+) pump activity, that controls cellular ionic homeostasis, seems to be reduced in aging. The contractions elicited by Na(+) pump inhibition with ouabain are negatively modulated by the release of a diffusible endothelial factor, an effect lost in aging, being replaced by an endothelium-dependent contracting factor that facilitates ouabain responses.