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Jonathan E. Graves, Nivedita Singh, Paul D. Taylor, Raymond J. MacAllister, Donald R. J. Singer, P-130: Selective impairment of bradykinin-mediated endothelium-dependent relaxation in small arteries in healthy older people, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Pages 72A–73A, https://doi.org/10.1016/S0895-7061(01)01680-6
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Abstract
Blood pressure increases with age in acculturated societies. Relaxation of small arteries in older people has been reported to be impaired but mechanisms for this are unclear. We therefore studied vaso-active pathways in small arteries dissected from sub-cutaneous fat biopsies from 31 healthy older subjects (age>60yrs) vs. 10 healthy younger controls (age 30-55 yrs) and mounted as vascular rings on an isometric small vessel myograph (Danish Myo Technology). Arteries from older subjects had a reduced maximal contraction to norepinephrine compared to younger controls (control 4.2±0.3(SEM) v. 3.3±0.2mN/mm; P<0.05). Maximal relaxation to the endothelium-dependent (ED) vasodilator bradykinin (BK) was significantly reduced in older subjects (BK AUC: controls 304±47; older 406±22; P<0.05). Vasodilatation to the endothelium-dependent agonist acetylcholine (ACh) and the endothelium-independent agonist sodium nitroprusside (SNP) was unaffected by age. Relaxation to acetylcholine was attenuated by the nitric oxide scavenger haemoglobin (ACh AUC: controls - 299±43; Hb - 460±49; P<0.05) but not by the nitric oxide synthase inhibitor L-NMMA. Both L-NMMA and Hb attenuated bradykinin relaxation. The cyclo-oxygenase inhibitor indomethacin did not alter responses to acetylcholine or bradykinin, however indomethacin combined with L-NMMA attenuated relaxation to ACh and BK.
In conclusion, isolated small arteries from healthy older subjects have impaired responses to norepinephrine and selective impairment of endothelium-dependent relaxation to bradykinin. For acetylcholine but not bradykinin it is suggested that relaxation may result in part from releasable stores of nitrosyl factors in the vascular endothelium. Our findings indicate that multiple inhibitors may be needed to unmask compensatory mechanisms for defects in endothelial function.
- acetylcholine
- nitric oxide
- norepinephrine
- indomethacin
- vascular rings
- biopsy
- blood pressure
- vascular endothelium
- vasodilators
- hemoglobin
- endothelium
- omega-n-methylarginine
- single nucleotide polymorphism
- prostaglandin-endoperoxide synthase
- bradykinin
- vasodilation
- nitroprusside sodium
- agonists
- nitric oxide synthase inhibitors
- older adult
- small blood vessel
- attenuation
