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.     

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.     

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.     

Examination of the fundus of the eye of renal hypertensive dogs

Summary Only 1 of 7 dogs with long-standing renovascular hypertension showed clear changes in the fundus. No distinct retinopathy was seen in the others. Ophthalmoscopy alone is thus of limited value in assessing the progress of benign hypertension in the dog.     

Vascular reactivity in chronic Goldblatt two kidney-one clip hypertensive rats

We studied the possible contribution of increased vascular reactivity in the chronic phase of Goldblatt two kidney-one clip hypertension. Vascular reactivity was evaluated in aortic strips from hypertensive rats (16 weeks after inducing hypertension) and age-matched control rats. The findings were: a) increased sensitivity to vasopressin in the aortic tissue of hypertensive rats, b) a similar response to angiotensin II, noradrenaline and KCl in hypertensive and control rats, and c) reduced maximal response to angiotensin II compared with other vasoconstrictors in both groups of rats. These results suggest a possible role for vasopressin in the chronic phase of this model of hypertension.     

Vascular reactivity in chronic Goldblatt two kidney-one clip hypertensive rats

Summary We studied the possible contribution of increased vascular reactivity in the chronic phase of Goldblatt two kidney-one clip hypertension. Vascular reactivity was evaluated in aortic strips from hypertensive rats (16 weeks after inducing hypertension) and age-matched control rats. The findings were: a) increased sensitivity to vasopressin in the aortic tissue of hypertensive rats, b) a similar response to angiotensin II, noradrenaline and KCl in hypertensive and control rats, and c) reduced maximal response to angiotensin II compared with other vasoconstrictors in both groups of rats. These results suggest a possible role for vasopressin in the chronic phase of this model of hypertension.The authors thank Ms Karen Shashok for revising the English style.     

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.     

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.     

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.     

Neues Verfahren zur experimentellen Erzeugung permanenten und reversiblen Hochdruckes durch standardisierte Kompression der Niere

Summary A new simple method for the production of experimental hypertension has been developed. Anoxæmia of the kidney has been produced by encapsulating the organ in tubes of acetyl cellulose. Development and degree of hypertension is directly depending on the ratio between size of kidney and tube, so that standard size tubes for definite animal weight may be used with high percentage of success.     

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension.

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.     

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension

The effects of methimazole, and antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.     

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.     

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

Summary 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.     

Beta-adrenoceptor blocking drugs, heart rate and genetic hypertension development in rats.

In spontaneously hypertensive rats (SHRs) chronically treated during their growth with beta-adrenoceptor blocking drugs, no correlation was found between the reduction in heart rate and the prevention of genetic hypertension development.     

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).     

Effects of neurochemical lesions restricted to spinal cord monoaminergic neurons on blood pressure and sympathetic activity of spontaneously hypertensive rats

Intraspinal (i.s.) injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine in newborn spontaneously hypertensive rats (SHR) resulted, in the adult animal (30-week-old), in a marked decrease of spinal cord noradrenaline (NA) or 5-hydroxytryptamine (5-HT) levels, respectively. Since both neurotoxin- and vehicle-injected rats developed full hypertension and had similar plasma catecholamine concentrations, it is concluded that in SHR neither spinal cord NA nor 5-HT play a major role in development and maintenance of hypertension.     

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.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2–4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls·min^–1) as measured using the single-injection [⁵¹Cr] EDTA method (2K1C UNSAT; 1.99±0.18 versus 2K1C SAT; 1.27±0.09, p<0.02; and versus SHAM CONTROL; 1.45×0.01; p<0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [¹²⁵I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6–8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.     

Endothelin

Endothelin-1 is the most potent vasoconstrictor agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other isoforms, termed endothelin-2 and endothelin-3, were subsequently identified, along with structural homologues isolated from the venom of Actractapis engaddensis known as the sarafotoxins. In this review, we will discuss the basic science of endothelins, endothelin-converting enzymes, and endothelin receptors. Only concise background information pertinent to clinical physician is provided. Next we will describe the pathophysiological roles of endothelin-1 in pulmonary arterial hypertension, heart failure, systemic hypertension, and female malignancies, with emphasis on ovarian cancer. The potential intervention with pharmacological therapeutics will be succinctly summarized to highlight the exciting pre-clinical and clinical studies within the endothelin field. Of note is the rapid development of selective endothelin receptor antagonists, which has led to an explosion of research in the field.