Contribution of Selected Vasoactive Systems to Blood Pressure Regulation in Two Models of Chronic Kidney Disease

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.

Download Full-text

SPECULATIONS ОN BLOOD PRESSURE INCREASE MECHANISMS IN RENAL ARTERY CLIPPED WISTAR RATS

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2013-19-3-221-226 ◽

2013 ◽

Vol 19 (3) ◽

pp. 221-226

Author(s):

N. V. Kuzmenko ◽

M. G. Pliss ◽

N. S. Rubanova ◽

V. A. Tsyrlin

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Renovascular Hypertension ◽

Wistar Rats ◽

Renal Denervation ◽

Renal Nerves ◽

Blood Pressure Elevation ◽

Sympathetic Nervous

Objective.To examine the mechanisms underlying the activation of the sympathetic nervous system and blood pressure elevation in vasorenal hypertension in the male Wistar rats weighing 250–300 g.Design and methods.We observed the development of renovascular hypertension, beat-to-beat interval and heart rate variability in animals with intact renal nerves and denervated ischemic kidney for 8 weeks after renal artery clamping. Eight weeks later after renal artery clamping in hypertensive rats with denervated ischemic kidney, both-sided renal denervation was performed, and blood pressure was monitored for 6 weeks.Results.Although the ischemic kidney denervation reduces the activity of the sympathetic nervous system, it does not prevent renovascular hypertension development. However, both-sided renal denervation leads to the normalization of blood pressure in the rats with stable renovascular hypertension.Conclusion.We suggest that increased afferent fl ow from structural formations of the ischemic kidney plays an important role for the increased sympathetic nervous system activity.

Download Full-text

Increased fibroblast growth factor-21 in chronic kidney disease is a trade-off between survival benefit and blood pressure dysregulation

Scientific Reports ◽

10.1038/s41598-019-55643-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Toshihiro Nakano ◽

Kazuhiro Shiizaki ◽

Yutaka Miura ◽

Masahiro Matsui ◽

Keisei Kosaki ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Nervous System ◽

Growth Factor ◽

Kidney Disease ◽

Sympathetic Nervous System ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Wild Type ◽

Sympathetic Nervous

AbstractCirculating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21−/− mice died earlier than wild-type mice. Paradoxically, these Fgf21−/− CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21−/− CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.

Download Full-text

Cardiovascular Risk in Chronic Kidney Disease: Role of the Sympathetic Nervous System

Cardiology Research and Practice ◽

10.1155/2012/319432 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 21

Author(s):

Jeanie Park

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Renal Failure ◽

Nervous System ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Sympathetic Nervous System ◽

Renal Disease ◽

Left Ventricular ◽

Sympathetic Nervous

Patients with chronic kidney disease are at significantly increased risk for cardiovascular disease and sudden cardiac death. One mechanism underlying increased cardiovascular risk in patients with renal failure includes overactivation of the sympathetic nervous system (SNS). Multiple human and animal studies have shown that central sympathetic outflow is chronically elevated in patients with both end-stage renal disease (ESRD) and chronic kidney disease (CKD). SNS overactivation, in turn, increases the risk of cardiovascular disease and sudden death by increasing arterial blood pressure, arrythmogenicity, left ventricular hypertrophy, and coronary vasoconstriction and contributes to the progression renal disease. This paper will examine the evidence for SNS overactivation in renal failure from both human and experimental studies and discuss mechanisms of SNS overactivity in CKD and therapeutic implications.

Download Full-text

The Influence of Neonatal Treatment with Guanethidine on the Development of Isolation-Induced Hypertension in Adult Rats

Clinical Science ◽

10.1042/cs0650469 ◽

1983 ◽

Vol 65 (5) ◽

pp. 469-474 ◽

Cited By ~ 2

Author(s):

S. M. Gardiner ◽

T. Bennett

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Wistar Rats ◽

Adult Rats ◽

Male And Female ◽

Neonatal Treatment ◽

Induced Hypertension ◽

Female Wistar Rats ◽

Sympathetic Nervous

1. Rats housed individually in glass metabolism cages develop hypertension. Since previous experiments have provided some evidence for the involvement of the sympathetic nervous system in the maintenance of the hypertension, the present work was designed to explore the possible involvement of the sympathetic nervous system in the genesis of isolation-induced hypertension. 2. Male and female Wistar rats were treated neonatally with guanethidine, with a protocol designed to produce an extensive peripheral sympathectomy; control rats received saline. 3. The effects of isolation on systolic blood pressure and fluid and electrolyte balances were studied when the rats were mature. 4. Guanethidine-treated rats did not develop hypertension in response to isolation whereas control rats did. 5. There were no significant differences between the fluid and electrolyte balances of the guanethidine-treated rats compared with controls throughout the period of isolation. 6. It is concluded that a fully functional sympathetic nervous system is required for the development of isolation-induced hypertension, but its involvement is not through a modulation of renal function.

Download Full-text

Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22105388 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5388

Author(s):

Germán Domínguez-Vías ◽

Ana Belén Segarra ◽

Manuel Ramírez-Sánchez ◽

Isabel Prieto

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Olive Oil ◽

Wistar Rats ◽

Virgin Olive Oil ◽

Renal Medulla ◽

Standard Diet ◽

Male Wistar Rats ◽

Sympathetic Nervous

High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.

Download Full-text

SYMPATHETIC HYPERACTIVITY IN CHRONIC KIDNEY DISEASE PATIENTS: FROM PATHOGENESIS TO TREATMENT

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.2(38).2013.11 ◽

2017 ◽

pp. 141-160

Author(s):

N. Stepanova

Keyword(s):

Chronic Kidney Disease ◽

Nervous System ◽

Kidney Disease ◽

Sympathetic Nervous System ◽

Crucial Role ◽

Clinical Relevance ◽

Cardiovascular Complications ◽

Current Treatment ◽

Sympathetic Hyperactivity ◽

Sympathetic Nervous

Sympathetic nervous system plays a crucial role in the development of cardiovascular complications in chronic kidney disease (CKD) patients. The aim of this review is to summarize up-to-date knowledge of the sympathetic hyperactivity in the pathogenesis of CKD, its clinical relevance, and as the options of current treatment.

Download Full-text

Renal Denervation Therapy (RDT) in Resistant Hypertension

BIRDEM Medical Journal ◽

10.3329/birdem.v2i2.12325 ◽

2012 ◽

Vol 2 (2) ◽

pp. 104-112

Author(s):

Mohammad Gaffar Amin ◽

Hasna Fahmima Haque

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Resistant Hypertension ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Antihypertensive Agents ◽

Radiofrequency Energy ◽

Sympathetic Nervous

Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite the use of three antihypertensive drugs including a diuretic. As much as one third of patients with arterial hypertension are treatmentrefractory as they do not reach sufficient blood pressure control despite combination antihypertensive therapy of significant duration. The hyperactivity of sympathetic nervous system (SNS) in the occurrence of treatment-resistant long standing hypertension has been established both in animal models and in clinical practice. In these patients, the kidneys play a central role as an activator of the sympathetic nervous system. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments based on old concepts. In the absence of orally active antihypertensive agents, patients with severe and complicated hypertension were widely treated by surgical denervation of the kidneys until the 1960s, but this approach was associated with a high incidence of severe adverse events and a high mortality rate. A new catheter system using radiofrequency energy has been developed, allowing an endovascular approach to renal denervation and providing patients, with resistant hypertension, with a new therapeutic option that is minimally invasive and can be performed rapidly under local anaesthesia. With this method the afferent and efferent sympathetic nervous fibers surrounding the renal artery are ablated precisely keeping the renal artery intact. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected resistant hypertensive patients with suitable renal artery anatomy. The available evidence suggests a significant and persistent blood pressure-lowering effect and a very low incidence of short & long term complications with no deleterious effects on renal function. These data, although promising, need confirmation in larger randomized controlled clinical trials with longerterm follow-up.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12325(Birdem Med J 2012; 2(2): 104-112)

Download Full-text

Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.1.95 ◽

1997 ◽

Vol 83 (1) ◽

pp. 95-101 ◽

Cited By ~ 147

Author(s):

Gang Bao ◽

Naira Metreveli ◽

Rena Li ◽

Addison Taylor ◽

Eugene C. Fletcher

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Adrenal Medulla ◽

Blood Pressure Response ◽

Episodic Hypoxia ◽

Sympathetic Nervous ◽

Renal Artery Denervation

Bao, Gang, Naira Metreveli, Rena Li, Addison Taylor, and Eugene C. Fletcher. Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system. J. Appl. Physiol. 83(1): 95–101, 1997.—Previous studies in several strains of rats have demonstrated that 35 consecutive days of recurrent episodic hypoxia (7 h/day) cause an 8- to 13-mmHg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. The present study was undertaken to further define the role of renal artery sympathetic nerves and the adrenal medulla in this BP increase. Male Sprague-Dawley rats had either adrenal medullectomy, bilateral renal artery denervation, or sham surgery. Rats from each of these groups were subjected to episodic hypoxia for 35 days. Control groups received either compressed air or were left unhandled. Adrenal demedullation or renal artery denervation eliminated the chronic diurnal mean BP response (measured intra-arterially) to episodic hypoxia, whereas sham-operated controls continued to showed persistent elevation of systemic BP. Plasma and renal tissue catecholamine levels at the end of the experiment confirmed successful adrenal demedullation or renal denervation in the respective animals. The chronic episodic hypoxia-mediated increase in diurnal BP requires both intact renal artery nerves as well as an intact adrenal medulla.

Download Full-text