Features of neurohumoral systems’ functional activity at a hypertensive crisis



According to modern concepts, hypertensive crisis [HC] is one of the most common and serious complications of hypertensive disease [HD]. It is characterized by acute, sharp increasing of the blood pressure [BP]. As a result of the hemodynamic instability a number of disorders of functional activity in various organs are developing and the most serious of them are acute cerebrovascular accident, pulmonary edema, myocardial infarction [1, 2].

In the development of HC the essential meaning have the increase of functional activity of the adrenergic system [3.4.5]. During the HC in the blood plasma of patients with a labile hypertensive disease [LHD] concentrations of adrenaline [A] and noradrenaline [NA] are significantly increased [6]. Strengthening the biosynthesis of NA is one of the mechanisms of high blood pressure support in HC patients. At the stable hypertonic diseases [SHD] increasing of adrenal systems' activity and a tendency to suppression of sympathetic-adrenal systems' [SAS] mediators synthesis are observed. SAS activity is determined not only by the absolute level of catecholamines, but also by the state of adrenergic receptor [7]. If the synthesis of catecholamine sensitive adrenergic receptor is suppressed, it can be regarded as a protective reaction [8.9.10]. With age, the amount of alpha- and beta-receptors of hypertensive patients' (HD and HC) is changing: the quantity of beta-receptors decreases while the alpha-receptors amount stay stable. There is a tone adaptation of arteries to lowering cardiac index [CI] and the threshold of sensitivity of baroreceptors [11]. A total peripheral vascular resistance [TPVR] is increased independently of the original nerve stimulus, which indicates the likely disease stabilization [12,13].

A number of researchers [14,15] also indicate the effect of increasing the concentration of NA in the blood plasma and reducing it to the myocardium on the intensity of left ventricular hypertrophy [LVH]. In other sources [16] in the patients during HC with the development of LVH, it is not marked activation of SAS and renin -angiotenzin-aldosterone system [RAAS].

Increased aldosterone in LHD patients during HC is related, according to the authors [17], to the increase in system activity of the pituitary-adrenal cortex. Corticosteroids cause the activation of synthesis of angiotensin-1 — changing enzyme, and this effect is mediated by receptors [18]. Some researchers [5] did not find significant differences of concentration of hormones of the adrenal cortex in hypertensive patients from healthy indicators. However, at the average age of patients the mineral- and glucocorticoid receptors were higher than in the elderly one, that determines the efficiency of hormonal influences.

Angiothensine simulating the production of corticosteroids in adrenal glands, regulates the synthesis of receptors. When low rennin form of HD with HC a violation of secretion, plasma concentrations and urinary excretion of some glucocorticoids [19] can be found. Other studies [14] in HD mark a significant decrease in cortisol — aldosterone index. RAAS activity at the HD depends on the stage of the disease [20,11]. In the development of the pressor mechanism of RAAS in HC the important pathogenetic role plays the initial action of renin.

High plasma renin activity [PRA] realizes its effect on blood pressure through vasoconstriction and sodium block effect of angiotensine II and angiotensine III. The level of renin at the HC is variable. Low ATM is a sign of hypervolemic form of HD [21]. According to the authors [3 [, for the low renin form of HD with HC, it is characterized by the low level of the blood plasma aldosterone concentration [PAC], unlike hypertension, associated with lesions of the adrenal gland. Analysis of clinical and physiological researches show, that HC with high PRA is characterized by more frequent cardiovascular complications [1,10].

When LHD, there is an increasing of the aldosterone predominantly in patients with normal and high PRA, with GBS — mostly at low PRA [23]. Associated with high levels of PRA activation mineral- and glucocorticoid adrenal function with a significant increase of aldosterone and plasma cortisol concentration is an important component in the pathogenesis of the syndrome of malignant hypertension with HD [24].

Endothelium reduces coronary blood flow, without exerting direct influence on the parameters of contractility and oxygen consumption. The mechanism of action of endothelium is rather complicated. There is no doubt, that in the genesis of the vascular wall response to the endothelium, a major role plays permeability canals for slow calcium current in the cell [28]. There was a significant decrease in vascular tonus and blood pressure after inhibition of nitric oxide, produced by the endothelium. In the development of vasospastic reactions, certain role may play the violation of the ratio of endothelium and nitrogen monoxide in the field of the local vascular damage [29]. Endothelial vascular cells and muscle-elastic types are involved in the synthesis and discharging of variety of biologically active substances, including vasodilators — endothelium, derived relaxing factor [EDRF] and prostacyclin [26]. In contrast to the EDRF, active principle of which is the nitrogen oxide, the relaxing effect of prostacyclin is due to the initiation system of adenylyl cyclase — periodic adenosine monophosphate [CPAM].

Stimulation of beta-adrenergic receptors increases CPAM concentration in the cell, alpha-adrenergic receptor — cycling guanosine monophosphate [ARCGM]. Calcium ions inhibit the enzyme of guanylate cyclase, increasing the content of the cell ARCGM. When HC the sensitivity of the system to ARCGM increases to hormonal cue on the background of CPAM oppression system [4]. Accumulation CPAM having a vasoconstrictor effect, can play a role in hypertrophy of smooth muscle cells and an increase in vascular resistance [14,11,30]. It is estimated, that CPAM can also influence on the process of hypertrophy, including indirectly through its activation by calcium cations of sarcoplasmic cells, phosphorylation of proteins with increased synthesis [27].

Prostaglandins [PG], having mainly local vasodilator effect, suppress the pressor effect of RAAS and limit the functional activity of the sympathetic nerves by inhibition of mediator release, play a significant role in the genesis of HC [31]. PG are involved in autoregulation of renal blood flow, sodium transport and water in the tubules, the mechanisms of development of salt and other kinds of diuresis [32]. PG can cause the restructuring of the cell membrane, which leads to a change in the activity of the enzyme membrane [14, 33]. Depressor PG impairs the conductivity for calcium of cell membranes of smooth muscle, slow down its transport into the cell [31]. As a result of numerous studies in the HD with HC the violations of the structure of the plasma membrane was revealed, as well as permeability to monovalent cations, decrease of calcium binding ability, combined with impaired calcium transportation systems with calcium overload of cells. Damage to the cell membrane is the common factor, which stimulates the formation and modifies the action of the released PG.

Membrane concept of HD pathogenesis confirms the validity of classification of the essential hypertension to the diseases of the imperfect adaptation at the cellular level, which made it possible to put forward the theory of «pathology of cellular membranes» [28].

PG E series inhibit the release of NA of nerve endings [32]. Reverse sympathetic neurotransmitter release inhibition is also associated with the PG effect on availability of calcium required for this. Low threshold dose of PGE 2, which causes a decrease in blood pressure, shows a high sensitivity to the arterial vascular bed to PGE 2 in hypertensive patients, which decreases with increase in duration of disease [35]. PGE during HC increases the activity of kininogenase — kinin system of blood [KKSB]. Acting directly to the smooth-muscle structure of the vascular wall, they cause relaxation and dilatation of vessels, thus reducing the TPR, improving myocardial contractile function, venous flow to the heart, stroke and minute volume [SV and MV / / 36,37,38]. When HC, it is detected a reduction in the formation of PGE2, more pronounced in the stabilization of blood pressure at a high level, was found to increase PGF2, PGE2 ratio, which indicates the relative dominance of pressor PGF2, PGE2 [37,39]. The renal PG changes revealed early in HD, may be the cause of increasing renal vessels resistance and increase the sodium content in the interstitial. Increased interstitial volume of kidney, in turn, affects the level of activity of the RAAS and KWWF [17].

In the extracellular fluid content, regulation atriums are involved, secreting atrial sodium uremic factor [SUF]. It plays an important role in the circulation and renal homeostasis in patients with essential hypertension [29, 21, 16]. SUF causes vascular relaxation, natriuresis and diuresis through the expansion of the renal vessels, inhibits the activity of the RAAS [30, 2, 22]. When HD with HC an increase in SUF content can be observed. After the infusion, the patient during the HD synthetic SUF [21], the prolonged decline in systolic blood pressure [SBP] is noted, mainly due to a decrease in the MO, the fluid movement from vessels into the extravascular space, a significant increase in the excretion of sodium and magnesium with an impact on the rate of glomerular filtration and urine output, decrease in PRA levels.

References:

1. Adams R. P. (2004). Juniperus deltoidеs, a new species and nomenclatural notes on Juniperus policarposand Juniperus turcomanica (Cupressaceae). Phytologia 86:49–53.
2. Andrews R. K., Berndt M. C. (2004). Platelet physiology and thrombosis // Thrombosis
3. Aggarwal M., Khan I. A. (2006). Hypertensive crisis: hypertensive emergencies and urgencies // Cardiol. Clin., 24(1):135–146.
4. Aronow W. S., Fleg J. L., Pepine C. J. et al. (2011) ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension // Journal of the American Society of Hypertension, 2011, 5 (4); 259–352.
5. Campbell N. R., Lackland D. T., Lisheng (2015) L. et al. Using the Global Burden of Disease study to assist development of nation-specific fact sheets to promote prevention and control of hypertension and reduction in dietary salt: a resource from the World Hypertension League // Journal of clinical hypertension (Greenwich, Conn.), 17 (3):165–7.
6. Chockalingam A. (2008) World Hypertension Day and global awareness // Canadian Journal of Cardiology, 24(6):441–44.
7. Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika SK, et al. (2009) Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the Trials of Hypertension Prevention follow-up study. Arch Intern Med. 2009 Jan 12;169(1):32–40.
8. Daugherty S. L., Powers J. D., Magid D. J. Incidence and prognosis of resistant hypertension in hypertensive patients // Circulation, 2012,125; 1635–42.
9. Drozda J. Jr., Messer J. V., Spertus J. et al. (2011) ACCF/AHA/AMA-PCPI 2011 Performance Measures for Adults With Coronary Artery Disease and Hypertension: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures and the American Medical Association-Physician Consortium for Performance Improvement // Circulation, 2011, 124(2); 248–70.
10. Esler M., Lambert E., Schlaich M. (2010) Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension». // J. Appl. Physiol., 2010, 109 (6); 1996–98.
11. Go A. S., Bauman M., King S. M. et al. (2013) An Effective Approach to High Blood Pressure Control: A Science Advisory From the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention // Hypertension 2013, 63 (4); 878–885.
12. Goldstein L. B., Bushnell C. D., Adams R. J. et al. (2011) Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association // Stroke, 2011, 42(2); 517–84.
13. Lackland D. T., Weber M. A. (2015) Global burden of cardiovascular disease and stroke: hypertension at the core // The Canadian journal of cardiology, 2015, 31 (5); 569–71.
14. Lehrmann, J.F. (2007) Knowledge Translation of ACEP Clinical Policy on Hypertension. //Annals of Emergency Medicine.-2007.-№ 14.-P.1090.
15. Mancia G., Fagard R., Narkiewicz K. et al. (2013) ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // European Heart Journal, 2013, 34 (28); 2159–219.
16. Mancia G., Fagard R., Narkiewicz K. (2013) ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // J. Hypertens, 2013, 31; 1281–57.
17. Marchesi C., Paradis P., Schiffrin E. L. et al. (2008) Role of the renin-angiotensin system in vascular inflammation // Trends Pharmacol. Sci., 2008, 29 (7); 367–74.
18. Marik P. E., Rivera R. (2011) Hypertensive emergencies: an update. //Curr. Opin. Crit. Care.-2011.-№ 17.-P.569–580.
19. Marik P. E., Varon J. (2007) Hypertensive crises: challenges and management // Chest, 2007, 131(6); 1949–62.
20. Marx J., Hockberger R., Walls R. Rosen’s Emergency Medicine, 8th ed. Mosby, 2013.
21. Matchar D. B., McCrory D. C., Orlando L. A. et al. (2008) Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension // Ann. Intern. Med., 2008, 148(1); 16–29.
22. Navar L.G. (2010) Activation of the intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension // J. Appl. Physiol., 2010, 109 (6); 1998–2000.
23. O’Connor R. E., Brady W., Brooks S. C. et al. (2010) Acute Coronary Syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. // Circ., 2010, 122; 787–817.
24. Ostchega Y., Dillon C. F., Hughes J. P. et al. (2004) Trends in hypertension prevalence, awareness, treatment, and control in older U. S. adults: data from the National Health and Nutrition Examination Survey 1988 to 2004 // Journal of the American Geriatrics Society, 2007, 55 (7); 1056–65.
25. Palatini P., Julius S. (2009) The role of cardiac autonomic function in hypertension and cardiovascular disease // Curr. Hypertens., 2009, 11 (3); 199–205.
26. Peacock W. F. et al. (2011). Hypertensive heart failure: patient characteristics, treatment, and outcomes // Am. J. Emerg. Med., 29:855–9.
27. Poulter N. R., Prabhakaran D., Caulfield M. (2015). Hypertension // Lancet, 386 (9995): 801–12.
28. Rodriguez M.A., Kumar S. K., Caro M. A. et al. (2010). Hypertensive crisis //Cardiol. Rev., 18(2):102–7.
29. Siu A. L. U.S. (2015). Screening for High Blood Pressure in Adults: U. S. Preventive Services Task Force Recommendation Statement // Annals of Internal Medicine, 163(10):778–86.
30. Turnbull F., Neal B., Ninomiya T. et al. (2008). Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomized trials // BMJ, 336 (7653):1121–3.
31. Versari D., Daghini E., Virdis A. et al. (2009). Endothelium-dependent contractions and endothelial dysfunction in human hypertension // Br. J. Pharmacol.,157 (4):527–36.
32. Wolff T., Miller T. Evidence for the reaffirmation of the U. S. (2007). Preventive Services Task Force recommendation on screening for high blood pressure // Ann. Intern. Med.,147(11):787–91.