Platelet abnormalities and the pathophysiology of essential hypertension

The mechanisms whereby intracellular calcium concentration is controlled are briefly reviewed. With the current knowledge of both calcium homeostasis and the function and properties of cellular Ca2+-target proteins/signal transduction systems, a dysfunction of cellular calcium metabolism is considered in relation to the pathogenesis of hypertension. Although the enhanced peripheral vascular resistance characteristic of hypertension is ultimately a function of Ca2+ availability for smooth muscle cell contraction, the platelet possesses many parallel biochemical and physiological properties. Therefore, we have utilized the platelet as the cell-model for investigating the role of Ca2+ in hypertension disorders. An overview of Ca2+-linked platelet processes altered in essential hypertension is presented, and an attempt is made to integrate these multiple aberrations in a fundamental membrane lesion.     

Phosphoinositide content in the erythrocyte membrane of rats with spontaneous and renal hypertension

Summary The increase of the content of triphosphoinositide in the erythrocyte membrane in rats with spontaneous and renal hypertension and decrease of phosphatidylinositol at spontaneous hypertension were revealed.     

Hypertension mediated by the activation of the rat brain 5-hydroxytryptamine receptor sites

Summary 5-Hydroxytryptamine (5-HT) administered intraventricularly (i.vent.) in rats produced hypertension without considerable changes in heart rate. After transsection of the spinal cord or i.vent. administration of methysergide, 5-HT failed to produce the pressor effect. Thus, the hypertension results from the activation of 5-HT receptor sites of the rat brain.This work was supported by Union of Scientific Medical Institutions of Serbia (Grant No. 85).     

Nature/nurture and the nature of nurture in the etiology of hypertension.

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blood-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Blood pressure and impairment of endothelium-dependent relaxation in spontaneously hypertensive rats

Summary Correlation between hypertension and impairment of endothelium-dependent relaxation was demonstrated using aortae from certain strains of rats with various levels of spontaneous hypertension. It was also observed that the impairment of endothelium-dependent relaxation is the secondary change due to hypertension, and the level and duration of hypertension is the determinant factor of the impairment.     

Effect of para-methoxyphenylethylamine on chronic stress-induced hypertension in the rat

This report presents data showing that par-methoxyphenylethylamine is effective in both preventing and reversing chronic stress-induced hypertension in the rat.     

Blood pressure and impairment of endothelium-dependent relaxation in spontaneously hypertensive rats

Correlation between hypertension and impairment of endothelium-dependent relaxation was demonstrated using aortae from certain strains of rats with various levels of spontaneous hypertension. It was also observed that the impairment of endothelium-dependent relaxation is the secondary change due to hypertension, and the level and duration of hypertension is the determinant factor of the impairment.     

Effect of para-methoxyphenylethylamine on chronic stress-induced hypertension in the rat

Summary This report presents data showing that para-methoxyphenylethylamine is effective in both preventing and reversing chronic stress-induced hypertension in the rat.     

Selective activation of noradrenergic neurons in the brainstem and spinal cord of young spontaneously hypertensive rats

Summary In young spontaneously hypertensive rats (SHR), dopamine -hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities were examined in the brainstem nuclei. Activation of noradrenergic neurons in the locus coeruleus, A2 and spinal intermediolateral cell areas, resulting in enhanced sympathetic nervous activity in the periphery, initiates hypertension. Adrenergic neurons, unchanged in these and A1 cell areas of young SHR, are not involved in the development of hypertension in SHR.     

Evidence of abnormalities in net sodium and potassium fluxes in erythrocytes of patients with essential hypertension]

A new and simple laboratory test for measuring net Na+ and K+ fluxes in Na+-loaded/K+-depleted human erythrocytes was developed and applied to hypertension. Moderate essential hypertension was characterized by a constant increase in net K+ influx; more severe cases showed a drop in net Na+ efflux. Na+ and K+ erythrocyte fluxes were found to be normal in hypertension of renal origin.     

Ouabain--a link in the genesis of high blood pressure?

Hypertension or high blood pressure is a risk factor that increases risk of myocardial infarction, renal failure or cerebral stroke. The pathogenesis of hypertension is due to a variety of causes, including inherited predisposition, dietary habits, especially salt intake, smoking, and also 'general lifestyle'. But for the scientist interested in the complex interplay of physiological and molecular factors, the actual causes of high blood pressure remain uninvestigated. The following article is concerned with new reports that ouabain, a plant derivative, occurs in human beings, in whom it appears to have a hormonal function; ouabain may even play a key role in the pathogenesis of hypertension. We are thus brought a step closer to the background of cardiovascular disease; we may also be afforded a lead to a new therapeutic principle.     

Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Ouabain — a link in the genesis of high blood pressure

Hypertension or high blood pressure is a risk factor that increases risk of myocardial infarction, renal failure or cerebral stroke. The pathogenesis of hypertension is due to a variety of causes, including inherited predisposition, dietary habits, especially salt intake, smoking, and also ‘general lifestyle’. But for the scientist interested in the complex interplay of physiological and molecular factors, the actual causes of high blood pressure remain uninvestigated. The following article is concerned with new reports that ouabain, a plant derivative, occurs in human beings, in whom it appears to have a hormonal function; ouabain may even play a key role in the pathogenesis of hypertension. We are thus brought a step closer to the background of cardiovascular disease; we may also be afforded a lead to a new therapeutic principle.     

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Effect of diazepam (Valium®) on chronic stress-induced hypertension in the rat

Summary Chronic treatment with diazepam was effective in preventing chronic stress-induced hypertension in rats. It also prevented the stressful stimuli from maintaining a hypertensive level in animals previously made hypertensive by chronic stress.     

Quantitative immunofluorescence of tyrosine hydroxylase in the adrenal medulla of spontaneously hypertensive rats

The amount of tyrosine hydroxylase protein in the adrenal medulla, which was estimated by a quantitative immunofluorescence method, was higher in spontaneously hypertensive rats than in normotensive control Wistar-Kyoto rats at 4 and 16 weeks of age before and after the development of hypertension.     

Can blockade of presynaptic adrenergic beta receptors explain the antihypertensive effects of propranolol?]

Pretreatment with 6-hydroxydopamine abolished the antihypertensive effects of intravenously and intracisternally administered dl-propranolol in dogs with acute neurogenic hypertension. These results show that the anti-hypertensive action of this drug is dependant on the integrity of central catecholaminergic neurones and suggest an action on presynaptic bêta-adrenoceptors.     

Maternal involvement in the development of cardiovascular phenotype

Over the past 20 years, laboratory studies of genetically defined animal models of human essential hypertension have provided valuable information on the pathophysiology of this disturbance in cardiovascular regulation. Relatively fewer studies have examined the impact of preweaning factors on the developing cardiovascular system of hypertensive animals. In our laboratory studies, we have utilized two inbred genetically hypertensive models: the spontaneously hypertensive (SHR) rat and its Wistar/Kyoto (WKY) normotensive control strain as well as the Dahl hypertension-sensitive (SS/Jr) and hypertension-resistant (SR/Jr) strains. To manipulate the preweaning maternal environment, we have employed the technique of reciprocal cross-fostering of litters between hypertensive and matched normotensive mothers. Our findings to date point to the maternal environment as a powerful influence on the development of high blood pressure in genetically hypertensive rats. In general, hypertensive rats reared by normotensive foster mothers have significant reductions in arterial blood pressure in adulthood. Thus, the progression of hypertinsive disease is not strictly predtermined by genotypic factors. Rather, a genetic predisposition to hypertension interacts with preweaning environmental factors to determine an animal's cardiovascular phenotype in adulthood.     

Variations in cardiac noradrenaline content during sodium loading in hypertension prone and resistant rats

Summary The cardiac catecholamine content of Sabra rats and their 2 genetically derived substrains, hypertension prone and resistant rats, was studied by high pressure liquid chromatography and electrochemical detection. Both in the control period and after sodium and DOCA administration the cardiac noradrenaline level is higher in hypertension resistant rats than in Sabra rats, and also higher than in hypertension prone rats. This finding suggests that a reduction of the cardiac sympathetic nervous tone is involved in the genetic resistance to sodium.     

Development of high blood pressure in spontaneously hypertensive rats is delayed by treatment with cyclosporin at an early age

In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.