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J Iwai

Publications and source records attributed to J Iwai.

119 records · Page 7Linked to original sources
PubMedDate not supplied

Gene expression of endothelin receptors in aortic cells from cyclosporine-induced hypertensive rats.

1. We examined preproendothelin-1, ETA and ETB receptor mRNA levels in aortic endothelial and smooth muscle cells from cyclosporine (CyA)-induced hypertensive rats using the reverse transcription polymerase chain reaction method. 2. Aortic endothelial preproendothelin-1 mRNA expression was about 1.5-fold higher, while that of ETB receptor mRNA was markedly decreased in CyA-treated rats compared with those in controls. 3. The expression of ETA receptor mRNA in smooth muscle cells from CyA-induced hypertensive rats was increased about two-fold over that in cells from control animals. 4. Thus, increased endothelial preproendothelin-1, and ETA receptor mRNA levels in smooth muscle cells, which are concomitant with the decrease in ETB receptor mRNA levels in endothelium, may contribute to CyA-induced hypertension in rats.

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PubMedDate not supplied

Cardiac output and peripheral resistance in strains of rats sensitive and resistant to NaCl hypertension.

The interrelationship of blood pressure, cardiac output, and peripheral resistance was studied in Dahl "S" and "R" rats after 3 days on a high (8%) NaCl diet. Both "S" and "R" rats were normotensive when fed a normal (0.3%) NaCl diet. After 3 days of the high NaCl diet, the "R" rats remained normotensive (BP 112 mm Hg), while the "S" rats had an elevation of arterial pressure (BP 133 mm Hg) (p less than 0.001). The cardiac outputs of both "S" and "R" rats were similar on the low NaCl diet. After 3 days of high NaCl feeding, the cardiac output of the "R" rats rose 18% above the "R" control level (p less than 0.0001), while the peripheral resistance declined 14% below the "R" control level (p less than 0.005), and the blood pressure (BP) did not change, a pattern quite contrary to the concept of "whole-body" autoregulation. With a similar 3-day high NaCl feeding in "S" rats, cardiac output (p less than 0.005) and peripheral resistance (p less than 0.05) both increased 10%, while BP rose 20%. After 7 days of high NaCl feeding, the cardiac output of the "S" rats had returned to normal, while blood pressure and peripheral resistance both continued to be elevated. This pattern of response in "S" rats could be compatible with the concept of "whole-body" autoregulation. However, since both NaCl hypertension and Goldblatt hypertension can occur in settings in which "whole-body" autoregulation appears not be to causally related, one cannot be certain whether "whole-body" autoregulation is playing a causal role in the mechanism of NaCl-induced hypertension in "S" rats. It is a striking dichotomy that 3 days of high salt feeding produces vasoconstriction in "S" rats and vasodilation in "R" rats.

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Effect of salt on prostaglandin metabolism in hypertension-prone and -resistant Dahl rats.

The effect of high salt intake on vascular and renomedullary prostaglandin (PG) synthesis was compared in Sprague-Dawley and salt-sensitive (S) and -resistant (R) Dahl rats. Animals were given a diet containing either 0.6% or 8% NaCl starting at 5 weeks of age, and were sacrificed 6 weeks later. Systolic blood pressure of S rats increased to 220 +/- 7 mm Hg but was unaffected in R and Sprague-Dawley rats. Prostaglandin synthesis was studied in aortic rings and renomedullary microsomes using 14C-arachidonate as substrate. [3H]PGE2 degradation was measured in the renocortical cytosol. In Sprague-Dawley and R rats, aortic PGI2 synthesis was not affected by high salt intake, while a significant increase compared to animals on 0.6% NaCl (from 608 +/- 84 to 992 +/-108 pmoles/60 min, p less than 0.05) was noted in S rats. Enhancement of PGI2 synthesis in S rats may be secondary to the hypertension. Salt-loading consistently stimulated renomedullary PGE2 synthesis in all three animal groups. S rats, however, had the lowest PG synthesis in renal medullas compared to Sprague-Dawley and R rats when placed on either diet. Thus, even after 6 weeks on high salt, S rats did not reach the levels of PGE2 synthesis seen in R or Sprague-Dawley rats on regular diet. The activity of cortical 15-hydroxyprostaglandin dehydrogenase was increased by salt-loading in S and Sprague-Dawley, but not in R rats. R rats had lower dehydrogenase activity than the other two groups when placed on either diet. The observed differences in PG synthesis and catabolism will tend to maintain the net output of renal PGs highest in R and lowest in S rats. These differences correlate with the reported differences in renal papillary flow between these two rat strains and may be relevant to their susceptibility or resistance to hypertension in response to salt.

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Potassium feeding reduces hyperactive central nervous system pressor responses in Dahl salt-sensitive rats.

Dahl showed that feeding KCl prevents the rise in blood pressure caused by a high NaCl diet in salt-sensitive Dahl "S" rats. Such S rats when normotensive on a low NaCl diet have a 2 to 3 times greater pressor response than Dahl "R" rats to intracerebroventricular hypertonic saline (600 mOsm/liter) or angiotensin II (AII) (500 ng). Does dietary KCl prevent NaCl hypertension in S rats partly by abolishing these hyperactive central nervous system (CNS) pressor responses? The effect of potassium-loading on CNS pressor responses was studied in S rats on a low (0.3%) NaCl diet. Drinking a 2% KCl solution reduced the CNS pressor responses in S rats to both AII and hypertonic saline by 44% (p less than 0.025) and brought them down almost as low as in R rats. KCl added to the low NaCl dry diet also decreased the CNS pressor responses in S rats to AII and to hypertonic saline by 39% (p less than 0.01) and 59% (p less than 0.02) respectively. K-citrate added to the low NaCl diet was generally as effective as KCl in reducing CNS pressor responses. K-citrate reduced the angiotensin pressor response by 44% (p less than 0.001) and the hypertonic saline pressor response by 46% (p less than 0.05). Thus, potassium feeding greatly diminished the hyperactive CNS pressor responses in S rats. This CNS action may well explain a good part of the protective effect of KCl against NaCl hypertension in S rats.

Angiotensin II↗
PubMedDate not supplied

Dahl S rats have increased natriuretic factor in atria but are markedly hyporesponsive to it.

Three experiments were carried out to determine whether atrial natriuretic factor (ANF) plays a part in Dahl hypertension. Results showed that ANF from both atria from 13 Dahl salt-sensitive (S) rats that had been fed a 4% NaCl diet for 12 weeks induced an average peak Na excretion of 23.0 muEq/min/g kidney in 13 Sprague-Dawley (SD) recipients vs 12.6 from atria from 13 salt-resistant (R) rats fed 4% NaCl (-45%, p less than 0.01), possibly indicating greater ANF secretion in S rats in order to enhance a reduced Na excretion. In 13 R rats, the ANF content in both atria increased from 14.0 after a 0.11% NaCl diet to 23.7 after 5 days of 4% NaCl diet (p less than 0.001) and then back to 12.6 after 12 weeks of 4% NaCl (p less than 0.001). Thus, ANF almost doubled after brief Na loading but returned to normal during continued Na loading. In S rats with a tendency to Na retention, ANF was elevated to about 23 in all three periods. ANF produced a 130-fold increase in natriuresis and a renal papillary plasma flow ( RPPF ) of 30.8 ml/min/100 g, 41% above the control level of 21.7, p less than 0.001. The marked increase in RPPF is very likely a partial cause of the natriuresis. A constant amount of ANF was continuously infused intravenously into 10 S rats and nine R rats all on 0.11% NaCl diets. Mean Na excretions in R and S were 5.3 and 4.6 muEq/min/100 g kidney before ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

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Potassium protection against lesions of the renal tubules, arteries, and glomeruli and nephron loss in salt-loaded hypertensive Dahl S rats.

Dahl S rats (20/group) were given three Purina diets for 24 weeks: 4% NaCl-no added potassium (BP 171 mm Hg); 4% NaCl-3.8% K citrate (BP 174 mm Hg); 4% NaCl-2.6% KCl (BP 173 mm Hg). The added potassium did not lower blood pressure (BP) but strikingly reduced microscopic renal lesions. Focal tubular dilation was scored blindly (100, severest lesions; 0, normal). Scores were: renal cortex: no potassium (41); K citrate (20); KCl (22), 50% improvement p less than 0.001; outer medulla: no potassium (79); K citrate (54); KCl (58), 30% improvement p less than 0.001; renal papilla: no potassium (49); K citrate (28); KCl (28), 43% improvement, p less than 0.001. Both K citrate and KCl also eliminated the thickened walls and relatively narrowed lumens of the hypertensive renal arterioles, without lowering BP. In these same rats, the wall thickness of arterioles from 20 normotensive salt-resistant (R) rats on 4% NaCl averaged 18.9 mu vs 26.1 mu in arterioles from 18 hypertensive salt-sensitive (S) rats on 4% NaCl with no added potassium. Adding either KCl or K citrate to the 4% NaCl diet strikingly reduced the wall thickness to that found in the R rat, even though the BP was not reduced at all. Potassium did not lower the high BP but apparently reduced the severity of the arteriolar lesions resulting from that high BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Cardiac hypertrophy and performance of Dahl hypertensive rats on graded salt diets.

The relationship between arterial pressure and left ventricular (LV) functional capacity and LV mass during the natural development of cardiac hypertrophy was assessed in Dahl-resistant (R) and -sensitive (S) hypertensive rats maintained on three dietary NaCl regimens (0.4%, 4.0%, and 8.0% for 9 weeks, then 4.0%) from 5 until 20 weeks of age. In R rats, arterial pressure and LV mass were unaffected by diet. In contrast, S rats demonstrated levels of arterial pressure and LV hypertrophy that were graded according to dietary NaCl. Hemodynamic studies on rats under ether anesthesia demonstrated that the graded pressure elevation in S rats was produced by corresponding increases in total peripheral resistance, as cardiac output did not vary. During acute volume loading, the S rats on all diets achieved the same maximum stroke volume as did R rats, despite the marked increase in the arterial pressure of S rats. An analysis of the ejection fraction/afterload relationship demonstrated preserved contractile state. The ability of the left ventricle to generate pressure was increased in S rats in direct proportion to the degree of LV hypertrophy. Thus, in young adult S rats, cardiac performance was well compensated since pump and contractile functions were maintained and pressure-generating capacity was increased in relation to the degree of LV hypertrophy.

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Hypertension-producing factor in serum of hypertensive Dahl salt-sensitive rats.

To investigate whether serum in hypertensive Dahl salt-sensitive rats (S rats) contains a hypertensinogenic substance, we examined the effects of repeated injections of serum from such S rats on blood pressure (BP) and pressor responses. Serum was collected from either hypertensive or normotensive S rats (fed an 8% or 0.11% NaCl diet, respectively) and injected into uninephrectomized recipient S rats for 2 weeks (0.45 ml, twice a day, i.v.). Serum from hypertensive rats injected for 14 days significantly increased BP by 14 mm Hg (143 vs 129, p less than 0.05), pressor responses to angiotensin II (ANGII) by 45% (p less than 0.005), pressor responses to norepinephrine (NE) by 38% (p less than 0.025), and Na concentration in the aortic wall of recipient rats by 5.9% (p less than 0.05), compared to the effects of the injection of serum from normotensive S rats. These results imply that hypertensive S serum contains a hypertensinogenic substance and that this serum factor produces a mild hypertension in the recipient rats and also contributes importantly to the hypertension in donor S rats. Dahl salt-resistant rats (R rats) on either 8% or 0.11% NaCl had normal BP. Their sera produced no differences in BP or in pressor responses in recipient rats. Hence 8% NaCl, which produced no hypertension, also induced no hypertensinogenic serum factors in R rats. We sought to determine whether nephrectomy would alter these humoral factors. The BP averaged 139 mm Hg in rats receiving normotensive sham-nephrectomized S serum vs 154 in those receiving hypertensive sham-nephrectomized S serum, 15 mm Hg higher (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMedDate not supplied

Potassium reduces cerebral hemorrhage and death rate in hypertensive rats, even when blood pressure is not lowered.

In a study of the effects of K+ in stroke prone spontaneously hypertensive rats, adding K+ to normal chow was found to reduce the mortality from 83% to 2%, a 98% reduction. An 86% reduction in mortality occurred even when blood pressure was virtually equal in the two stroke prone spontaneously hypertensive groups being compared. Dietary K+ supplements also reduced mortality in hypertensive Dahl salt-sensitive rats from 55% to 4%, a 93% reduction. There was an 87% reduction in mortality even when blood pressure was equal in the Dahl salt-sensitive groups being compared. The added dietary K+ decreased blood pressure moderately in stroke prone spontaneously hypertensive rats and modestly in Dahl salt-sensitive rats, which probably contributed to the reduced death rate. More importantly, however, the added K+ seemed to prevent severe lesions in cerebral arteries and deaths even when blood pressure lowering was eliminated as a protective factor. In another group of stroke prone spontaneously hypertensive rats, there was a 40% incidence of cerebral hemorrhage in surviving rats not receiving K+ supplements and no incidence of cerebral hemorrhage in similar surviving rats receiving K+ supplements, which suggests that K+ supplements confer protection against brain hemorrhage.

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