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Increase, Vascular Resistance leads to Hypertension
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Hypertension is characterized partly by elevated systemic vascular resistance which is caused by alterations to vascular tone (towards vasoconstriction) over time (Lee and Griendling, 2008). As blood vessels constrict, the available volume in the vessel lumen for blood flow is restricted, resulting in elevated blood pressure.
Note : The role of the heart in the maintenace (and change) of blood pressure over time is not part of this AOP, however it is of critical importance for the development of hypertension.
Evidence Supporting this KER
It is well-established that increased systemic vascular resistance (SVR), increased vascular stiffness and increased vascular reactivity contribute to the pathophysiology of hypertension (Foëx and Sear, 2004; Mayet and Hughes, 2003; Brandes et al., 2014); thus biological plausibility is strong for increased SVR leading to hypertension. This is observed in patients with hypertension (Chan et al., 2016).
Uncertainties and Inconsistencies
One study showed that infusion of L-NMMA (6 mg/kg) resulted in increased SVR and only a modest increase in blood pressure. Changes in diastolic blood pressure were observed to be more pronounced in healthy men, than systolic blood pressure (Brett et al., 1998), and infusion of L-arginine (an eNOS substrate) had no significant effect.
As mentioned above, other AOPs are necessary to capture understanding and assess the evidence surrounding the roles of the heart, kidney and nervous system in order to get the full picture of the linkage between chronic changes in SVR and hypertension.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Studies supporting this key event relationship were performed in humans and rats.
Brandes, R.P. (2014). Endothelial dysfunction and hypertension. Hypertension 64, 924–928.
Brett, S.E., Cockcroft, J.R., Mant, T.G., Ritter, J.M., and Chowienczyk, P.J. (1998). Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise. J. Hypertens. 16, 429–435.
Chan, S.S., Tse, M.M., Chan, C.P., Tai, M.C., Graham, C.A., and Rainer, T.H. (2016). Haemodynamic changes in emergency department patients with poorly controlled hypertension. Hong Kong Med. J. Xianggang Yi Xue Za Zhi Hong Kong Acad. Med. 22, 116–123.
Foëx, P., and Sear, J.W. (2004). Hypertension: pathophysiology and treatment. Contin. Educ. Anaesth. Crit. Care Pain 4, 71–75.
Haynes, W.G., Noon, J.P., Walker, B.R., and Webb, D.J. (1993). Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J. Hypertens. 11, 1375–1380.
Lee, M.Y., and Griendling, K.K. (2008). Redox signaling, vascular function, and hypertension. Antioxid. Redox Signal. 10, 1045–1059.
Mayet, J., and Hughes, A. (2003). Cardiac and vascular pathophysiology in hypertension. Heart Br. Card. Soc. 89, 1104–1109.
McVeigh, G.E., Allen, P.B., Morgan, D.R., Hanratty, C.G., and Silke, B. (2001). Nitric oxide modulation of blood vessel tone identified by arterial waveform analysis. Clin. Sci. Lond. Engl. 1979 100, 387–393.
Nakmareong, S., Kukongviriyapan, U., Pakdeechote, P., Kukongviriyapan, V., Kongyingyoes, B., Donpunha, W., Prachaney, P., and Phisalaphong, C. (2012). Tetrahydrocurcumin alleviates hypertension, aortic stiffening and oxidative stress in rats with nitric oxide deficiency. Hypertens. Res. Off. J. Jpn. Soc. Hypertens. 35, 418–425.
Silva, B.R., Pernomian, L., and Bendhack, L.M. (2012). Contribution of oxidative stress to endothelial dysfunction in hypertension. Front. Physiol. 3, 441.
Stamler, J.S., Loh, E., Roddy, M.A., Currie, K.E., and Creager, M.A. (1994). Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 89, 2035–2040.
Wilkinson, I.B., MacCallum, H., Cockcroft, J.R., and Webb, D.J. (2002). Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo. Br. J. Clin. Pharmacol. 53, 189–192.