The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain). A characteristic feature of the ISIAH strain is an increase in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the normotensive Wistar albino Glaxo (WAG) rats, and no differences were found in plasma corticosterone. However, the 0 . 5-h restraint stress produced higher activation of the adrenal cortex in the ISIAH rats. Gluco-and mineralocorticoid responses to the blood volume reduction stresses and ACTH and corticosterone responses to social stress were stronger in the ISIAH than in the control WAG rats. An increase in epinephrine content in adrenals in the basal state and enhanced response of the sympathetic adrenal medullary system to handling stress were observed in the ISIAH rats. Restraint stress produced significantly higher expression of genes encoding corticotropinreleasing hormone-mRNA in hypothalamus and proopiomelanocortin-mRNA in pituitary in the ISIAH than in the WAG rats. Restraint stress produced a decrease in glucocorticoid receptor (GR) gene expression (GR-mRNA) in hippocampus in the ISIAH, but not in the WAG rats. A persistent increase in tyrosine hydroxylase-mRNA in adrenals of the ISIAH rats was found. It is concluded that the ISIAH rat strain is an appropriate model of stress-sensitive hypertension with the predominant involvement of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems in its pathogenesis.

Norepinephrine (NE) and epinephrine (Epi) concentrations in arterial plasma and in skin tissue were measured chromatographically before and after external cooling. Urethan-anesthetized rats were cooled either slowly (0.004–0.006°C/s) or rapidly (0.03– 0.05°C/s). Blood samples were drawn three times from each animal: 1) before cooling and at a rectal temperature decreased 2) by 0.5°C and 3) by 3–4°C. Skin samples were taken from controls and from rapidly or slowly cooled rats at a rectal temperature lowered by 0.5°C. The resting mean values were 36.7 ± 0.3°C for rectal temperature, 0.62 ± 0.079 and 1.09 ± 0.203 ng/ml for plasma NE and Epi, and 85.6 ± 4.1 and 137.6 ± 34.3 ng/g for skin NE and Epi. A decrease in rectal temperature by 0.5°C at rapid cooling produced a 2.6-fold increase of NE and a 2.8-fold increase of Epi in plasma. Concomitantly, there was a significant decrease in skin NE concentration by 28% and Epi by 86%. At a rectal temperature decreased by 0.5°C after slow cooling, plasma catecholamines did not change; at unaltered skin NE concentration, there was a reduction in skin Epi concentration (60%). When rectal temperature was lowered by 3–4°C, the increase in plasma NE was virtually the same at both cooling rates and only plasma Epi increased more after deep rapid cooling than slow cooling. Thus the sympathoadrenal system may be differently activated depending on cooling rate. Rapid cooling, when the dynamic activity of the skin cold receptors is involved in the cold response, may provide conditions for an earlier activation of the sympathoadrenal system. This may evidence the functional significance of the dynamic activity of the skin cold receptors in the formation of the cold defense responses.

The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and on the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5-HT and a lower level of its metabolite, 5-HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5-HIAA/5-HT ratio in various brain regions differed considerably, the decrease of the 5-HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41-45% of control values), with the exception of the frontal cortex, where the decrease of the 5-HIAA/5-HT was somewhat smaller (to 54%). The presence of the remaining 45% +/- 1.9% of the control ratio value indicates rather effective oxidative deamination of 5-HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5-HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures.

Myocardial norepinephrine (NE) is considered a meaningful parameter for estimation of cardiac function. Long lasting changes in myocardial NE appear to be not only a consequence of pathologic processes in the myocardium, but may be a factor responsible for some diseases (e.g. increased propensity for arrhythmias or negative effect on left ventricular contractility in congestive heart failure). In this respect monitoring of myocardial NE is of great importance. A microdialysis sampling technique coupled with liquid chromatography with electrochemical detection (LCEC) was developed to measure the in vivo NE concentration in the myocardial interstitium of conscious, freely moving rats. LCEC using a dual-electrode amperometric detection in the series configuration provided detection limits for NE of 10 pg/ml in 20 μl microdialysis samples. Microdialysis probes of the linear design were implanted in the myocardial tissue in the periphery of the left descending coronary artery. The basal steady-state concentration of NE in myocardial dialysate of awake, freely moving rats was found to be 0.17 ± 0.026 ng/ml. Delivery through the microdialysis probe of the NE reuptake inhibitor desipramine (DMI) at a concentration of 0.1 mM increased NE release to 153 ± 13% of control. If the concentration of DMI in the perfusate was increased to 1.0 mM, NE release increased to only 166 ± 21% of control.

ISIAH rats may serve as a living proof that stress may produce sustained hypertension, and genetically determined enhanced stress responsiveness of corticosterone and, especially, aldosterone may play a crucial role in the mechanism of hypertension development.