Inherited Stress-induced Arterial Hypertension Research Articles

All signs of metabolic syndrome in the hypertensive ISIAH rats are associated with increased activity of transcription factors PPAR, LXR, PXR, and CAR in the liver

It is known that the metabolic syndrome (MS), which includes hypertension, dislipidemia, glucose intolerance, and obesity leads to cardiovascular diseases. The MS risk is growing catastrophically. Molecular mechanisms allowing to understand the reason of integrated dysfunctions, taking place at MS cases, have remained almost unstudied. The chronical stress plays a crucial role in MS development; therefore in the present work a hypertensive rat strain with Inherited Stress-Induced Arterial Hypertension (ISIAH) was used as a model. It was shown that ISIAH rat strain as compared with the control WAG rat strain is characterized by increased content of triglyceride, VLDL and LDL cholesterols, a decreased content of HDL cholesterol, a high level of apolipoprotein B-100, and decreased level of apolipoprotein A-I. The ISIAH rats body weight was higher as compared with WAG rats; ISIAH rats blood glucose content was higher too. Thus, strain hypertension for ISIAH rat is accompanied by dislipidemia, increased glucose content, and increased body weight, representing a whole set of MS signs. Since at MS cases the systemic abnormalities in lipid and carbohydrate metabolism take place, the functional activity of transcription factors (TFs) participating in integral regulation of lipid and carbohydrate metabolism genes in liver was measured. PPAR, LXR, PXR, CAR DNA-binding activity was increased in ISIAH rats, suggesting involvement of these TFs in MS development. Integrated investigation of PPAR, LXR, PXR, CAR regulatory mechanisms, signal transduction and transcriptional targets will provide insights into the pathogenesis of MS and offer valuable information for designing of drugs for MS treatment.

Genetic Control of the Corticosterone Level at Rest and Under Emotional Stress in ISIAH Rats with Inherited Stress-Induced Arterial Hypertension

The genetic background of the regulatory systems of the hypothalamic-pituitary-adrenal (HPA) axis in hypertension remains unclear. The inherited stress-induced arterial hypertension (ISIAH) and Wistar Albino Glaxo (WAG) normotensive rats were bred and their F2 progeny were used in a quantitative trait loci (QTL) analysis to identify genomic regions for plasma basal and stress-induced corticosterone levels, and for absolute and relative adrenal gland weights. The significant loci were found for stress-induced corticosterone on chromosome 9 and for adrenal weight on chromosome 6. The results may help to identify the genes controlling the trait phenotypes in the ISIAH rats characterized by the enhanced responsiveness to stressful stimulation.

Activity of 11β-hydroxysteroid dehydrogenase of rat kidney and liver in inherited stress-induced arterial hypertension

11beta-hydroxysteroid dehydrogenase (11beta-HSD) is the key enzyme of glucocorticoid metabolism, which catalyzes interconversion of corticosterone and 11-dehydrocorticosterone in rat. The activity of 11beta-HSD in kidneys of rats with inherited stress-induced arterial hypertension (ISIAH) was significantly (p < 0.05) higher than that in WAG rats. The opposite was observed in the activity of liver 11beta-HSD. Under stress condition no changes in the kidney 11beta-HSD activity of both strains were observed, but the liver 11beta-HSD activity in ISIAH rats was significantly (p < 0.05) higher as compared to basal level and stressed WAG rats. It is possible that the features of the 11beta-HSD activity in ISIAH rats may reflect the hypertensive status of ISIAH rats.

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adrenals, and systemic endocrine parameters were studied in ISIAH of different ages and compared to normotensive Wistar albino Glaxo (WAG) rats. Native organs were obtained for Western and PCR analysis. Perfusion-fixed organs were prepared for histopathology and quantitative histochemistry. Plasma renin and adrenal hormones were measured. Renal morphology was unaltered in ISIAH. The hypothalamic-pituitary-adrenocortical (HPA) axis was constitutively upregulated with enlarged adrenal cortices and enhanced plasma corticosterone levels. Plasma renin activity was not different between groups, whereas aldosterone levels were in part reduced. Juxtaglomerular NO synthase type 1, cyclooxygenase type 2, and renin expression were significantly reduced, whereas tubular gene products related to sodium transport (bumetanide-sensitive Na, K, 2Cl cotransporter type 2; thiazide-sensitive Na, Cl cotransporter; epithelial Na channel-alpha; 11beta-hydroxysteroid dehydrogenase type 2) were increased. These data suggest enhanced volume conservation by the kidney. Our data define ISIAH as an attractive model for the renal components determining salt and water homeostasis in hypertension. The specific condition of a basally stimulated HPA axis is highlighted, including the option to study effects superimposed by emotional stress.

Immediate and long-lasting effects of chronic stress in the prepubertal age on the startle reflex

The immediate and long-lasting effects of two models of chronic stress during the prepubertal period of life (21–32 days) on the acoustic startle response (ASR) were studied in outbred Wistar normotensives and rats with inherited stress-induced arterial hypertension (ISIAH) derived from them. Chronic variable stress (CVS) and repeated handling were used as chronic treatment. The obtained data showed a significantly attenuated ASR and a greater magnitude of prepulse inhibition (PPI) in juvenile and adult ISIAH compared to Wistar rats. The immediate effects of prolonged stress on the ASR were genotype-dependent. Young ISIAH rats exposed to both types of prepubertal stimulation had higher ASR than the age-matched controls. No significant stress-induced changes in the ASR were found in young Wistar rats. The long-lasting consequences of prolonged prepubertal stress were similar in the two strains and were determined by the specificity of stress stimulation: chronic handling had no effect on the ASR, while CVS enhanced it. The long-lasting effect of CVS experienced in prepubertal life appears to produce ASR changes similar to those seen in patients with posttraumatic stress disorder (PTSD). The magnitude of PPI increased from early age to adulthood and it was tolerant to environmental influences. The two rat strains did not differ in the rate of short-term habituation to repeated acoustic stimuli, which was unaffected by prepubertal stress. Evidence was obtained indicating that genetic and environmental background in childhood may contribute to the truncation of the startle response.