Altered Vascular Reactivity to Circulating Angiotensin II in Familial Hypercholesterolemia.
Adult
Angiotensin II
/ administration & dosage
Arterial Pressure
/ drug effects
Brachial Artery
/ drug effects
Case-Control Studies
Female
Forearm
Humans
Hyperlipoproteinemia Type II
/ blood
Infusions, Intravenous
Laser-Doppler Flowmetry
Male
Microcirculation
/ drug effects
Middle Aged
Skin
/ blood supply
Time Factors
Vasodilation
/ drug effects
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
30
01
2021
accepted:
29
06
2021
pubmed:
17
7
2021
medline:
12
2
2022
entrez:
16
7
2021
Statut:
ppublish
Résumé
We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.
Identifiants
pubmed: 34269699
doi: 10.1097/FJC.0000000000001106
pii: 00005344-202110000-00008
doi:
Substances chimiques
Angiotensin II
11128-99-7
Banques de données
EudraCT
['2010-024590-39']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
551-559Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:56–64.
Nickenig G, Jung O, Strehlow K, et al. Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression. Am J Physiol. 1997;272(6 pt 2):H2701–H2707.
Pollock DM. Endothelin, angiotensin, and oxidative stress in hypertension. Hypertension. 2005;45:477–480.
Solini A, Santini E, Ferrannini E. Enhanced angiotensin II-mediated effects in fibroblasts of patients with familial hypercholesterolemia. J Hypertens. 2005;23:367–374.
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.
Montezano AC, Nguyen Dinh CatCat AA, Rios FJ, et al. Angiotensin II and vascular injury. Curr Hypertens Rep. 2014;16:431.
van der Linde NA, Sijbrands EJ, Boomsma F, et al. Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity: a randomized trial with fluvastatin. Hypertension. 2006;47:1125–1130.
Tripathi A, Nadel ER. Forearm skin and muscle vasoconstriction during lower body negative pressure. J Appl Physiol (1985). 1986;60:1535–1541.
Feihl F, Liaudet L, Waeber B, et al. Hypertension: a disease of the microcirculation? Hypertension. 2006;48:1012–1017.
Noon JP, Walker BR, Webb DJ, et al. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest. 1997;99:1873–1879.
Steckelings UM, Wollschläger T, Peters J, et al. Human skin: source of and target organ for angiotensin II. Exp Dermatol. 2004;13:148–154.
Gössl M, Mitchell A, Lerman A, et al. Endothelin-B-receptor-selective antagonist inhibits endothelin-1 induced potentiation on the vasoconstriction to noradrenaline and angiotensin II. J Hypertens. 2004;22:1909–1916.
Mitchell A, Rushentsova U, Siffert W, et al. The angiotensin II receptor antagonist valsartan inhibits endothelin 1-induced vasoconstriction in the skin microcirculation in humans in vivo: influence of the G-protein beta3 subunit (GNB3) C825T polymorphism. Clin Pharmacol Ther. 2006;79:274–281.
Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020;46:1105–1108.
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–1418.
Fernandez-Nieto D, Jimenez-Cauhe J, Suarez-Valle A, et al. Characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the COVID-19 outbreak. J Am Acad Dermatol. 2020;83:e241.
Jörneskog G, Kahan T, Ekholm M, et al. Altered vascular responses to circulating angiotensin II in familial combined hyperlipidemia. J Cardiovasc Med (Hagerstown). 2008;9:1037–1044.
Charakida M, Tousoulis D, Skoumas I, et al. Inflammatory and thrombotic processes are associated with vascular dysfunction in children with familial hypercholesterolemia. Atherosclerosis. 2009;204:532–537.
Gooding KM, Hannemann MM, Tooke JE, et al. Maximum skin hyperaemia induced by local heating: possible mechanisms. J Vasc Res. 2006;43:270–277.
Leahy MJ, de Mul FF, Nilsson GE, et al. Principles and practice of the laser-Doppler perfusion technique. Technol Health Care. 1999;7:143–162.
Nilsson GE, Tenland T, Oberg PA. Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow. IEEE Trans Biomed Eng. 1980;27:597–604.
Caspary L, Creutzig A, Alexander K. Biological zero in laser Doppler fluxmetry. Int J Microcirc Clin Exp. 1988;7:367–371.
Ekholm M, Kahan T, Jörneskog G, et al. Haemostatic and inflammatory alterations in familial hypercholesterolaemia, and the impact of angiotensin II infusion. J Renin Angiotensin Aldosterone Syst. 2015;16:328–338.
Carlson K. Lipoprotein fractionation. J Clin Pathol Suppl (Assoc Clin Pathol). 1973;5:32–37.
Lopes-Virella MF, Stone P, Ellis S, et al. Cholesterol determination in high-density lipoproteins separated by three different methods. Clin Chem. 1977;23:882–884.
Nawawi H, Osman NS, Annuar R, et al. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin. Atherosclerosis. 2003;169:283–291.
Strawn WB, Chappell MC, Dean RH, et al. Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia. Circulation. 2000;101:1586–1593.
Nickenig G. Should angiotensin II receptor blockers and statins be combined? Circulation. 2004;110:1013–1020.
Banach M, Penson PE, Fras Z, et al. Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic. Pharmacol Res. 2020;158:104891.
Nickenig G. Central role of the AT(1)-receptor in atherosclerosis. J Hum Hypertens. 2002;16(suppl 3):S26–S33.
Veerkamp MJ, de Graaf J, Stalenhoef AF. Role of insulin resistance in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2005;25:1026–1031.
Yki-Jarvinen H, Westerbacka J. Insulin resistance, arterial stiffness and wave reflection. Adv Cardiol. 2007;44:252–260.
ter Avest E, Holewijn S, Bredie SJ, et al. Pulse wave velocity in familial combined hyperlipidemia. Am J Hypertens. 2007;20:263–269.
Junyent M, Zambón D, Gilabert R, et al. Carotid atherosclerosis in familial combined hyperlipidemia associated with the APOB/APOA-I ratio. Atherosclerosis. 2008;197:740–746.
Bishop VS, Sanderford MG. Angiotensin II modulation of the arterial baroreflex: role of the area postrema. Clin Exp Pharmacol Physiol. 2000;27:428–431.
Zhang Z, Rhinehart K, Solis G, et al. Chronic ANG II infusion increases NO generation by rat descending vasa recta. Am J Physiol Heart Circ Physiol. 2005;288:H29–H36.
Kellogg DL Jr. In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol (1985). 2006;100:1709–1718.
Gohlke P, Pees C, Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension. 1998;31(1 pt 2):349–355.
Vuorio A, Watts GF, Kovanen PT. Familial hypercholesterolaemia and COVID-19: triggering of increased sustained cardiovascular risk. J Intern Med. 2020;287:746–747.
Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020;22:95–97.
Iannuzzi A, Bianciardi G, Faccenda F, et al. Correction of erythrocyte shape abnormalities in familial hypercholesterolemia after LDL-apheresis: does it influence cerebral hemodynamics? Heart Vessels. 1997;12:234–240.
Dupont PA, Sirs JA. The relationship of plasma fibrinogen, erythrocyte flexibility and blood viscosity. Thromb Haemost. 1977;38:660–667.
Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related severe hypercoagulability in patients admitted to Intensive Care Unit for acute respiratory failure. Thromb Haemost. 2020;120:998–1000.
Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020;116:1666–1687.
Halperin RO, Sesso HD, Ma J, et al. Dyslipidemia and the risk of incident hypertension in men. Hypertension. 2006;47:45–50.
Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982;62:347–504.