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.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.     

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.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

Summary The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.Acknowledgment. The authors wish to acknowledge the assistance of Mark Kunneman and Elaine Hughes. This work was supported by the following grants: American Heart Association (Texas Affiliate) and National Institutes of Health HL 23815, HL 25349 and HL 24585.     

The effect of vasoactive agents on nutritive collateral circulation in rat muscles

Summary The relationship between the collateral and control nutritive blood flow (⁸⁶Rb) of the triceps muscle was not influenced by vasoactive agents (phenylephrine, angiotensin II, vasopressin) in the rat. Isolevine caused vasodilation only in the control muscle.     

Hemodynamic studies in a parabiotic model of portal hypertension

Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413 +/- 26 vs 318 +/- 23 ml X min-1 X kg-1; p less than 0.05) and portal venous inflow (9.61 +/- 1.29 vs 6.33 +/- 0.36 ml X min-1 X 100 g b.wt-1; p less than 0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension.     

The involvement of the renin-angiotensin system in the regulation of cell proliferation in the rat endometrium

Oestrogens are known to enhance angiotensin biosynthesis by increasing the elaboration of its precursor, angiotensinogen. On the other hand, we found that inhibition of angiotensin-converting enzyme (ACE) suppressed the proliferative response of the rat anterior pituitary gland to oestrogens. To answer the question whether the angiotensin system is involved in the control of the cell proliferation of the uterine epithelium, the effects of an ACE inhibitor, enalapril maleate, and of angiotensins II and IV, alone or together with losartan, an antagonist of angiotensin receptor type 1 (AT1), on endometrial epithelial cell proliferation have been studied. The experiments were performed on ovariectomized female Wistar rats. In the first experiment the animals were injected with a single dose of oestradiol benzoate or received an injection of solvent only. Half of the oestrogen-treated rats were injected additionally with enalapril maleate (EN, twice daily). The incorporation of bromodeoxyuridine (BrDU) into endometrial cell nuclei was used as an index of cell proliferation. It was found that oestradiol alone dramatically increased the BrDU labelling index (LI) of endometrial cell nuclei, and this effect was partially blocked by the simultaneous treatment with EN. In the second experiment, the animals were injected intraperitoneally with angiotensin II (AII), angiotensin IV (AIV) or saline, alone or together with losartan. It was found that AIV induced an increase in the LI in uterine epithelium, and this effect was not blocked by the simultaneous treatment with losartan. The increase in LI in uterine epithelium was also observed in the rats treated with AII and with losartan. These findings suggest an involvement of angiotensin IV in the control of uterine epithelium cell proliferation. Received 12 October 1998; received after revision 6 January 1999; accepted 2 February 1999     

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 hypertensive disease is not strictly predetermined by genotypic factors. Rather, a genetic predisposition to hypertension interacts with preweaning environmental factors to determine an animal's cardiovascular phenotype in adulthood.     

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.     

Inhibition of isoprenaline-induced increase in plasma renin concentration by vasoconstrictors.

The vasoconstrictors angiotensin II, vasopressin and the alpha-sympathomimetic phenylephrine significantly inhibit the renin release caused by the beta-sympathomimetic isoprenaline. The mechanism of the inhibition is discussed.     

Hemodynamic studies in a parabiotic model of portal hypertension

Summary Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413±26 vs 318±23 ml·min^–1·kg^–1; p<0.05) and portal venous inflow (9.61±1.29 vs 6.33±0.36 ml·min^–1·100 g b.wt^–1; p<0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension.Acknowledgment. The authors express their appreciation to Martha Shea for technical assistance.     

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.     

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.     

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased, alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.     

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.     

Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip.

Crude kallikrein (Padutin), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.     

Antidiuretic effects of oxytocin in the Brattleboro rat

The antidiuretic activity of oxytocin (OT) was measured in Brattleboro rats with congenital diabetes insipidus. A dose dependent antidiuretic response was found in animals receiving chronic infusions of 0.1 micrograms/h, 1.0 micrograms/h, and 5 micrograms/h of OT. OT infused at the rate of 5 micrograms/h over a 7-day period completely reversed the symptoms of diabetes insipidus. The results support the concept that OT serves as a weak agonist of vasopressin at the level of the kidney and at pharmacological levels exhibits antidiuretic activity.     

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.     

Action,in vitro et in vivo,de l'angiotensine II sur le captage cardiaque de la noradrénaline

Summary The action of angiotensin II on cardiac uptake of norepinephrine was investigated in the rat in vivo and in vitro. In contrast to desipramine, neither infusion of subpressive (10 ng/kg/min) or pressive (50–150 ng/kg/min) amounts of angiotensin on intact and/or binephrectomized rats, nor incubation of cardiac slices with angiotensin II (10^–5; 10^–9 M) impair the accumulation of tritiated norepinephrine and the level of metabolites. It is thus concluded that there is no inhibiting action of angiotensin II on the cardiac uptake of norepinephrine.     

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

Summary 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.This study was supported by grants from the Ministry of Education, Science and Culture, Japan (No. 59570018). Reprint requests to I.N., Department of Anatomy, School of Medicine, Fujita-Gakuen Health University, Toyoake, Aichi 470-11 (Japan).