Development Of Salt Hypertension Research Articles

Is renal ß-adrenergic-WNK4-NCC pathway important in salt hypertension of Dahl rats?

In 2011 Fujita and coworkers proposed that ß-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents. The aim of our study was to investigate whether the above hypothesis is also valid for salt hypertension of Dahl rats, which are characterized by high sympathetic tone and abnormal renal sodium handling. Male 8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats were fed either low-salt diet (LS, 0.4 % NaCl) or high-salt diet (HS, 4 % NaCl) for 6 weeks. Half of the animals on either diet were chronically treated with non-selective ß-blocker propranolol (100 mg/kg/day). At the end of the experiment diuresis and sodium excretion were measured prior and after hydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.). Furthermore, blood pressure (BP), heart rate (HR), sympathetic (pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kg i.v.) BP components were determined. Chronic HS diet feeding increased BP through sympathoexcitation in SS/Jr but not in SR/Jr rats. Concomitant propranolol treatment did not lower BP in either experimental group. Under the conditions of low salt intake HCTZ increased diuresis, natriuresis and fractional sodium excretion in SR/Jr but not in SS/Jr rats. HS diet feeding attenuated renal response to HCT in SR/Jr rats, whereas no HCTZ effect was observed in SS/Jr rats fed HS diet. Propranolol treatment did not modify diuresis or natriuresis in any experimental group. In conclusions, our present data do not support the idea on the essential importance of renal ß-adrenergic-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats.

Chronic antioxidant therapy lowers blood pressure in adult but not in young Dahl salt hypertensive rats: the role of sympathetic nervous system

It is well-known that salt hypertension is associated with increased oxidative stress. Since the development of salt hypertension is age-dependent, we were interested whether young and adult salt hypertensive Dahl rats differ in oxidative stress level and/or in the effects of chronic antioxidant therapy on blood pressure (BP) level and on the participation of particular vasoconstrictor/vasodilator systems in BP maintenance. Young (5-week-old) and adult (12-week-old) salt-sensitive (Dahl-S) male rats were fed high-salt diet (5% NaCl) and drank tempol solution (2 mm) for 5 weeks. BP was monitored with radiotelemetry and vasoconstrictor/vasodilator balance was evaluated at the end of experiment. Moreover, NO synthase activity, superoxide production and lipoperoxidation were determined in heart, kidney and aorta in separate subgroups of Dahl rats. Tempol treatment had quite opposite BP effects in young and adult Dahl-S rats. While it tended to increase BP in young salt hypertensive Dahl-S rats, it significantly lowered BP in the adult ones due to reduced sympathetic vasoconstriction. Importantly, high salt intake substantially reduced NO synthase activity in heart and kidney, and markedly increased superoxide production in kidneys and aorta of adult Dahl-S rats in which BP correlated positively with superoxide production in thoracic aorta and lipoperoxidation in kidneys. Chronic antioxidant therapy lowered BP only in adult salt hypertensive Dahl-S rats in which superoxide levels were increased in both kidneys and aorta. Blood pressure reduction induced by chronic tempol treatment is related to attenuated sympathetic vasoconstriction rather than to augmented NO-dependent vasodilatation.

Age-Dependent Salt Hypertension in Dahl Rats: Fifty Years of Research

Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension - salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of renin-angiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the salt-sensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake. On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals.

Chronic endothelin A receptor blockade attenuates contribution of sympathetic nervous system to salt hypertension development in adult but not in young Dahl rats

Endothelin-1 (ET-1) plays an important role in the pathogenesis of salt-dependent forms of hypertension in adult rats, but its participation in salt hypertension elicited in immature rats is still unknown. Therefore, we compared ET-1 role in the development or the maintenance of salt hypertension induced in young (4-week-old) or adult (12-week-old) Dahl rats. The contribution of pressor ET-1 effects to the maintenance of high blood pressure (BP) was studied using acute injection of ET(A) receptor antagonist ambrisentan (BSF 208075, 1 mg kg(-1) iv) to young or adult rats with established salt hypertension. Furthermore, using chronic ambrisentan treatment (30 mg kg(-1) day(-1) in the drinking fluid during 5 weeks of high salt intake), we investigated the age-dependent involvement of ET(A) receptors in salt hypertension development in these two age groups. Acute ET(A) receptor blockade lowered BP in both age groups of salt hypertensive Dahl rats more than in rats fed a low-salt diet (but without any age-dependent difference). Chronic ET(A) receptor blockade strongly attenuated the development of salt hypertension and cardiac hypertrophy in adult rats, but it had no significant effects on salt hypertension in young animals. Pronounced BP reduction induced in adult salt hypertensive rats by chronic ambrisentan treatment was attributed to attenuated sympathetic BP component, without changes in nitric oxide (NO)-dependent BP regulation. In contrast, chronic ambrisentan treatment of young animals did not modify sympathetic BP component but substantially attenuated NO-dependent vasodilatation. ET(A) receptor-mediated ET-1 effects play an important role in salt hypertension of adult but not young Dahl rats.

Transient cyclooxygenase inhibition blocks development of chronic angiotensin II‐salt hypertension

Hypertension (HT) is the major risk factor for cardiovascular diseases. Previously, cyclooxygenase inhibition with ketoprofen was found to prevent Angiotensin II (AngII)‐salt HT development and sympathetic over‐activity. But ketoprofen did not reverse established HT. Recently, Johnson and colleagues reported that transient, short‐term exposure to circulating AngII can “prime” (i.e. accentuate) subsequent AngII HT development. So we hypothesized that an early increase in cyclooxygenase activity accentuates AngII‐salt HT; additionally, we attempted to determine the time‐course of the effect. Radio‐telemetric recording of arterial pressure (AP) in a 22‐day protocol was made. After 3 days of control recordings, rats on 2% NaCl diet were pretreated with vehicle or ketoprofen (2mg/kg, sc) for 5 days and 11 days. From day 8, all rats received AngII (150 ng/kg/min, sc). In vehicle‐treated rats MAP rose to 147±2 mmHg. In rats pretreated with ketoprofen for 5 days and 11 days, MAP rose to 129±8 mmHg (p>0.05) and 109±7 mmHg (p<0.05) compared to vehicle treated rats. The fall in MAP using ganglionic blocker hexamethonium in 11‐day ketoprofen treated rats (35±7mmHg) was less than in vehicle treated rats (61±5mmHg) and 5‐day ketoprofen treated rats (70±2mmHg). We conclude that early AngII‐mediated cyclooxygenase pathway activation is critical for the later full development of AngII‐salt sympathoexcitation and HT.

Chronic endothelin A receptor blockade attenuates contribution of sympathetic nervous system to salt hypertension development in adult but not in young Dahl rats

Chronic endothelin A receptor blockade attenuates contribution of sympathetic nervous system to salt hypertension development in adult but not in young Dahl rats

Preventive dietary potassium supplementation in young salt-sensitive Dahl rats attenuates development of salt hypertension by decreasing sympathetic vasoconstriction

Increased potassium intake attenuates the development of salt-dependent hypertension, but the detailed mechanisms of blood pressure (BP) reduction are still unclear. The aims of our study were (i) to elucidate these mechanisms, (ii) to compare preventive potassium effects in immature and adult animals and (iii) to evaluate the therapeutic effects of dietary potassium supplementation in rats with established salt hypertension. Young (4-week-old) and adult (24-week-old) female salt-sensitive Dahl rats were fed a high-salt diet (5% NaCl) or a high-salt diet supplemented with 3% KCl for 5 weeks. The participation of vasoconstrictor (renin-angiotensin and sympathetic nervous systems) and vasodilator systems [prostanoids, Ca(2+) -activated K(+) channels, nitric oxide (NO)] was evaluated using a sequential blockade of these systems. Preventive potassium supplementation attenuated the development of severe salt hypertension in young rats, whereas it had no effects on BP in adult rats with moderate hypertension. Enhanced sympathetic vasoconstriction was responsible for salt hypertension in young rats and its attenuation for potassium-induced BP reduction. Conversely, neither salt hypertension nor its potassium-induced attenuation were associated with significant changes of the vasodilator systems studied. The relative deficiency of vasodilator action of NO and Ca(2+) -activated K(+) channels in salt hypertensive Dahl rats was not improved by potassium supplementation. The attenuation of enhanced sympathetic vasoconstriction is the principal mechanism of antihypertensive action exerted by preventive potassium supplementation in immature Dahl rats. Dietary potassium supplementation has no preventive effects on BP in adult salt-loaded animals or no therapeutic effects on established salt hypertension in young rats.

Relationships between membrane lipids and ion transport in red blood cells of Dahl rats

Distinct changes of membrane lipid content could contribute to the abnormalities of ion transport that take part in the development of salt hypertension in Dahl rats. The relationships between lipid content and particular ion transport systems were studied in red blood cells (RBC) of Dahl rats kept on low- and high-salt diets for 5 weeks since weaning. Dahl salt-sensitive (SS/Jr) rats on high-salt diet had increased blood pressure, levels of plasma triacylglycerols and total plasma cholesterol compared to salt-resistant (SR/Jr) rats. Furthermore, RBC of SS/Jr rats differed from SR/Jr ones by increased content of total membrane phospholipids, but membrane cholesterol was not changed significantly. SS/Jr rats had higher RBC intracellular Na + (Na i +) content and enhanced bumetanide-sensitive Rb + uptake. RBC membrane content of cholesterol and phospholipids correlated positively with RBC Na i + content, with the activity of Na +–K + pump and Na +–K +–2Cl − cotransport and also with Rb + leak. The content of phosphatidylserines plus phosphatidylinositols was positively associated with RBC Na i + content, with the activity of Na +–K + pump and Na +–K +–2Cl − cotransport and with Rb + leak. The content of sphingomyelins was positively related to Na +–K +–2Cl − cotransport activity and negatively to ouabain-sensitive Rb +–K + exchange. We can conclude that observed relationships between ion transport and the membrane content of cholesterol and/or sphingomyelins, which are known to regulate membrane fluidity, might participate in the pathogenesis of salt hypertension in Dahl rats.

Hypertensive response to chronic NG-nitro-L-arginine methyl ester (L-NAME) treatment is similar in immature and adult Wistar rats.

The aim of our study was to evaluate whether the blood pressure (BP) response to chronic inhibition of NO synthase (NOS) is exaggerated in young rats, which were reported to develop a more pronounced salt hypertension than the adult ones. The enhanced BP rise in immature rats subjected to excess salt intake might be due either to a generally increased reactivity in immature organisms to these stimuli or to a greater impairment of NO bioavailability that accompanies the development of salt hypertension. To determine between the two alternatives, we have compared the hypertensive response and the extent of NOS inhibition in immature (4-week-old) and adult (12-week-old) male Wistar rats which were treated with NG-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg of body mass per day) for 4 weeks. BP and NOS activity in the aorta, left ventricle and kidney were determined at the end of the experiment. It should be noted that chronic L-NAME treatment caused a similar degree of NOS inhibition in both age groups (irrespective of tissue examined). There was no significant difference in BP elevation between young and adult animals chronically treated with L-NAME. A strong negative correlation between NOS activity and BP level was observed in separate groups of normotensive controls and L-NAME hypertensive rats. Thus the BP of both normotensive and hypertensive animals seems to be inversely proportional to the production of NO. It can be concluded that there was the same BP rise in both age groups of L-NAME-treated rats in which a similar degree of NOS inhibition was disclosed. This suggests that the altered NO bioavailability (but not the generally exaggerated reactivity to hypertensive stimuli) is the cause of exaggerated hypertensive response observed in immature rats exposed to excess salt intake.

Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in early phases of salt hypertension development

Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been reported to be altered in both human essential and rat spontaneous hypertension. The aim of our study was not only to search for the occurrence of such alterations in platelets of rats with salt-induced hypertension but also to investigate whether these changes might precede blood pressure rise in this form of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal values and thrombin-induced changes of [Ca2+]i and pHi were determined in platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and SBN rats, whereas pHi was significantly lower in SBH than in SBN animals. Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which reflects the opening of a particular subclass of thrombin-operated Ca2+ channels, was similar in both strains. The moderate hypertension elicited in SBH rats by high salt intake was not associated with major alterations of basal [Ca2+]i or pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to thrombin in either strain. In contrast, high salt intake reduced thrombin-induced Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated positively with systolic but not with diastolic blood pressure. This could be ascribed to a very close relationship of basal [Ca2+]i values with pulse pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra rats with salt-dependent genetic hypertension differ from those described in essential hypertensive patients or rat strains with spontaneous forms of genetic hypertension. Our study also indicated that alterations of platelet [Ca2+]i do not precede blood pressure elevation in salt hypertension.

Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in early phases of salt hypertension development

Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been reported to be altered in both human essential and rat spontaneous hypertension. The aim of our study was not only to search for the occurrence of such alterations in platelets of rats with salt-induced hypertension but also to investigate whether these changes might precede blood pressure rise in this form of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal values and thrombin-induced changes of [Ca2+]i and pHi were determined in platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and SBN rats, whereas pHi was significantly lower in SBH than in SBN animals. Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which reflects the opening of a particular subclass of thrombin-operated Ca2+ channels, was similar in both strains. The moderate hypertension elicited in SBH rats by high salt intake was not associated with major alterations of basal [Ca2+]i or pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to thrombin in either strain. In contrast, high salt intake reduced thrombin-induced Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated positively with systolic but not with diastolic blood pressure. This could be ascribed to a very close relationship of basal [Ca2+]i values with pulse pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra rats with salt-dependent genetic hypertension differ from those described in essential hypertensive patients or rat strains with spontaneous forms of genetic hypertension. Our study also indicated that alterations of platelet [Ca2+]i do not precede blood pressure elevation in salt hypertension.

Glucocorticoid-induced cataract of developing chick embryo as a screening model for anticataract agents

Distinct changes of membrane lipid content could contribute to the abnormalities of ion transport that take part in the development of salt hypertension in Dahl rats. The relationships between lipid content and particular ion transport systems were studied in red blood cells (RBC) of Dahl rats kept on low- and high-salt diets for 5 weeks since weaning. Dahl salt-sensitive (SS/Jr) rats on high-salt diet had increased blood pressure, levels of plasma triacylglycerols and total plasma cholesterol compared to salt-resistant (SR/Jr) rats. Furthermore, RBC of SS/Jr rats differed from SR/Jr ones by increased content of total membrane phospholipids, but membrane cholesterol was not changed significantly. SS/Jr rats had higher RBC intracellular Na+ (Nai+) content and enhanced bumetanide-sensitive Rb+ uptake. RBC membrane content of cholesterol and phospholipids correlated positively with RBC Nai+ content, with the activity of Na+–K+ pump and Na+–K+–2Cl− cotransport and also with Rb+ leak. The content of phosphatidylserines plus phosphatidylinositols was positively associated with RBC Nai+ content, with the activity of Na+–K+ pump and Na+–K+–2Cl− cotransport and with Rb+ leak. The content of sphingomyelins was positively related to Na+–K+–2Cl− cotransport activity and negatively to ouabain-sensitive Rb+–K+ exchange. We can conclude that observed relationships between ion transport and the membrane content of cholesterol and/or sphingomyelins, which are known to regulate membrane fluidity, might participate in the pathogenesis of salt hypertension in Dahl rats.

Effects of dietary calcium on the development of salt hypertension in young and adult Dahl rats.

The effect of dietary calcium on the development of salt hypertension was studied in young and adult Dahl rats. Age-dependent development of blood pressure was compared in salt-sensitive (DS) and salt-resistant (DR) Dahl rats that were fed either a low-calcium (0.15%) or a high-calcium (2.5%) diet. Systolic blood pressure was consistently higher in DS rats than in a comparable group of DR rats. In young DS rats the high-calcium diet transiently attenuated the development of hypertension, whereas in adult rats this diet potentiated the development of hypertension. In young DS rats total plasma calcium was increased by the high-calcium diet, but in adult rats it was significantly decreased. Our results suggest that the effects of dietary calcium supplementation on calcium metabolism and the development of salt hypertension in DS rats depend on the age at which calcium supplementation is started.

Sympathetic nervous system and age-dependent salt hypertension in Brattleboro rats.

The effects of early sympathectomy on the development of salt hypertension were studied in prepubertal and adult rats with hereditary diabetes insipidus (DI). Early guanethidine administration caused a pronounced and long-term destruction of sympathetic nervous system (SNS) in Brattleboro rats in which blood pressure (BP) was significantly decreased until the age of 22 weeks. This SNS impairment did not abolish the age-dependent BP response of salt-loaded rats that was still greater in young than in adult sympathectomized DI rats. BP of young uninephrectomized DI rats was higher in the late than in the early phase of salt hypertension development. The early sympathectomy lowered BP and increased mortality in all groups of saline drinking DI rats except young uninephrectomized animals in which hypertensive response was attenuated but not prevented. It could be suggested that 1) increased BP response of young rats to high salt intake occurs even in animals with attenuated principal pressor systems, 2) the effects of early sympathectomy on the development of salt hypertension depend on the actual hemodynamic pattern, and 3) moderate BP increase might be a part of homeostatic mechanisms defending the organism threatened by chronic salt overload.

Age-dependent blood pressure response to increased salt intake in rats influenced by a transient renal ischaemia.

The influence of renal dysfunction (induced by ischaemic injury) on the development of salt hypertension was studied in rats which were exposed to 60 min of renal ischaemia when either immature or adult. Saline-drinking age-matched animals served as controls. The blood pressure, plasma urea concentration, extracellular fluid volume (ECFV) and renal mass were measured 21 and 50 days after renal ischaemia. Increments of plasma urea concentration and ECFV were considered to be indicators of renal dysfunction. Increased renal mass was used as an estimate of the degree of renal injury. In adult rats, both plasma urea concentration and ECFV were increased 3 weeks after renal ischaemia. This correlated with a pronounced increase of renal mass. A similar relation of renal mass to ECFV was still present 50 days after renal ischaemia. In rats treated when immature the increment of plasma urea concentration was much smaller and ECFV did not differ significantly from the control volumes. A mild salt hypertension developed only in those rats which were treated when immature. On the other hand, the blood pressure tended to decrease in animals treated when adult. It is concluded that mild renal dysfunction facilitates the development of salt hypertension in immature rats. This is in contrast with the reversed effects of extensive renal dysfunction in adult animals. It is suggested that the age of animals is more important for the induction of salt hypertension than the degree of renal dysfunction.

The effect of chemical damage to the renal medulla on its antihypertensive function.

Renomedullary antihypertensive function was studied in rats in which the renal medulla was chemically damaged either by chronic ingestion of high doses of aspirin (the rats were treated for 6 months before the experiment with aspirin at 300 mg/kg/day) or by a single injection of bromethylamine hydrobromide (BEA) (50 mg/rat, i.v., two months before the experiment). The results were compared to those from control, nontreated rats. When placed on a high salt intake (1% NaCl solution was offered instead of drinking water), the rats with aspirin-induced renomedullary damage and the controls did not develop hypertension during the 12-week period of salt loading, while the animals treated with BEA developed high blood pressure (systolic pressure over 20 kPa) by the sixth week. In the second experiment, renal medullae taken from control, aspirin-treated, and BEA-treated rats were transplanted to rats with chronic one-kidney one-clip hypertension, and the potency of medulla taken from the three different groups in lowering blood pressure in the hypertensive recipients was compared. A significant decrease in blood pressure of about 4–5 kPa was observed in the hypertensive rats which received transplants of medullae taken from control and aspirin-treated rats; whereas no significant change in blood pressure was observed in the hypertensive rats which received transplants of medullae taken from BEA-treated rats, or which were sham-transplanted. The results indicate that the deficiency of renomedullary antihypertensive function is an event conducive to the development of salt hypertension in rats, i.e., an increase in blood pressure in response to salt loading was observed only in animals in which the antihypertensive function of the medulla was decreased, as determined by the inability of renomedullary transplants to lower blood pressure in hypertensive recipients. Furthermore, the present data indicate that aspirin-induced renomedullary damage does not abolish renomedullary antihypertensive function; and thus the notion that hypertension associated with aspirin abuse nephropathy results from aspirin-induced renomedullary deficiency appears to be unlikely.

Age-dependent salt hypertension in Brattleboro rats: a hemodynamic analysis.

The hemodynamic effects of 0.6% saline, consumed either from youth (4th week of age) or from adulthood (12th week of age), were studied in unanesthetized, unoperated, and uninephrectomized homozygous female Brattleboro rats. Long-term saline drinking induced a general decrease of blood pressure in unoperated rats which was more pronounced in rats drinking it from youth. The relation of low systemic resistance and high cardiac output (observed at the age of 10-15 weeks) to the high mortality of these rats was discussed. Two phases were recognized in the development of salt hypertension in uninephrectomized rats drinking saline from youth. The increased systemic resistance played a major role during the early phase (13-15 weeks), while changes of body fluids as well as altered arterial compliance contributed to the elevation of systolic blood pressure in the late phase of salt hypertension (20-30 weeks of age). In uninephrectomized rats drinking saline from adulthood, the late blood pressure response was only slightly attenuated in comparison with uninephrectomized rats drinking saline from youth. The absence of increased arterial rigidity in the former group was the only major hemodynamic difference between these two groups of uninephrectomized rats aged 20-30 weeks.

Potentiating effect of gonadectomy performed in immature male rats on the development of salt hypertension.

Salt hypertension develops more rapidly and the final level of blood pressure is much higher in male rats castrated on the first day of life than in untreated animals or in rats castrated as adults.

Experimental Studies on Dietary Elements which Suppress the Development of Salt Hypertension (I)

Experimental Studies on Dietary Elements which Suppress the Development of Salt Hypertension (I)

Experimental Studies on Dietary Elements which Suppress the Development of Salt Hypertension (II)

Experimental Studies on Dietary Elements which Suppress the Development of Salt Hypertension (II)