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Notes: 1. Amplification of the entire first intron of the renin gene of spontaneously hypertensive rat (SHR), Wistar-Kyoto (WKY) and Sprague-Dawley rats (SD) followed by Bgl II digestion uncovered a new deletion (∼50 bp) which exists upstream of the SHR renin gene first intron tandem repeat element.2. The SHR tandem repeat element was 600 bp shorter than that in the WKY while the WKY tandem repeat element was 280 bp shorter than that in the SD.3. Since elements regulating gene expression are known to exist in the first intron of other genes, this new restriction fragment length polymorphism (RFLP) might play a role in the reported overexpression of the SHR renin gene independent of changes in the length of the tandem repeat element.

Notes: 1. It has been reported that the first intron of the renin gene of the spontaneously hypertensive rat (SHR) is shorter than that of the Wistar-Kyoto (WKY) rat, suggesting a role for this difference in the development of hypertension.2. The genealogy of some Australian SHR colonies has raised doubts about its similarity to the Japanese, American and European colonies.3. The polymerase chain reaction (PCR) technique has been used with primers identical to the flanking region of the first intron of the renin gene to determine its length in SHR, WKY and Sprague-Dawley (SD) from an Australian colony.4. The size of the first intron of the renin gene in SHR, WKY and SD was found to be approximately 3870, 4550 and 5000 base pairs, respectively, results which agree with those previously published.5. It was concluded that the first intron deletion, and its size, has been conserved in an Australian SHR colony.

Notes: 1. Four single base mutations unique to the spontaneously hypertensive rat (SHR) were identified in the first 1100 base pairs of its renin gene first intron when compared to that of Wistar-Kyoto and Sprague-Dawley normotensive rats.2. These mutations were found to fall within the consensus sequences for a number of transcription factors and thus may alter the affinity of these putative transcription factor binding sites.3. The reported overexpression of the renin gene in the SHR may therefore result from these structural abnormalities and, in turn, result in a tissue angiotensin-dependent hypertension in this strain.

Notes: 1. To examine whether the uterine environment plays a role in the development of hypertension in the spontaneously hypertensive rats (SHR), we have compared fetal weight, placental weight, and amniotic fluid composition of SHR and Wistar-Kyoto (WKY) rats after 20 days of gestation.2. Pregnant SHR and WKY were anaesthetized at 20 days of gestation and the uterus and embryonic sacs removed. Fetal and placental weights were recorded and amniotic fluid collected for measurement of volume, osmolality and electrolyte composition.3. No significant difference was found in litter size and placental weight between SHR and WKY. Total embryonic sac weight and fetal weight of SHR were significantly lower than WKY. Amniotic fluid volume, sodium concentration and osmolality of SHR were significantly higher than WKY, while amniotic fluid potassium concentration of SHR was significantly lower than WKY.4. Thus, the SHR foetus was significantly underweight compared to the WKY and was bathed in amniotic fluid with a significantly higher osmolality and sodium concentration. As the mature foetus is known to drink amniotic fluid, it is hypothesized that the elevated Na/K ratio in SHR amniotic fluid may instigate or accelerate the hypertensive process.

Notes: 1. It has been shown previously that low salt diet, confined to the perinatal period only, reduces blood pressure (BP) and sodium retention in spontaneously hypertensive rat (SHR) offspring at maturity when compared with those given high salt diet.2. In this study it is shown that such high salt diets are associated with an increased level of circulating Na-K-ATPase inhibitor (CINK) activity.3. Animals given perinatal high salt diet have a significantly greater tubular reabsorptive capacity when compared with those given low salt diet.4. The finding of a high level of circulating Na-K-ATPase inhibitory material in the face of increased renal tubular capacity and blood pressure suggests that while this inhibitory material may play a role in the elevated blood pressure of animals given high salt diet, it cannot cause the elevated rate of fluid reabsorption.

Notes: 1. Blood pressure, sodium excretion and salt taste were examined in Sprague Dawley (SD) and Munich Wistar (MW) rats exposed prenatally to either a high salt (2.3% NaCl w/w) or control diet.2. There was no significant difference in blood pressure at 2, 6 or 12 months between high salt and control groups in either strain. Similarly there was no significant difference in sodium excretion following a saline load by gavage (150 mmol/l, 1.5% BW).3. Munich Wistar rats which received high salt diet prenatally exhibited a reduced saline preference when offered a choice between water and 150 mmol/l NaCl as drinking fluid. There was no significant difference in saline preference between Sprague Dawley rats which received the high salt or control diet.4. Prenatal exposure to high salt diet failed to alter the blood pressure or excretion of a salt load in either SD or MW rats. In MW rats but not SD high salt diet prenatally resulted in a reduced saline preference at 3 months of age.

Notes: 1. The effect of oral captopril (30 mg/kg per day) on the blood pressure, plasma aldosterone concentration, urinary electrolytes and brain angiotensin-converting enzyme activity of spontaneously hypertensive rats of the Okamoto strain was examined.2. Over a seven day period, captopril caused a progressive fall in blood pressure with increased sodium excretion and urine volume and a significant fall in plasma aldosterone concentration.3. Following captopril, angiotensin converting enzyme activity increased significantly in the midbrain and medulla oblongata; the pituitary level of angiotensin converting enzyme activity was significantly decreased.4. The hypotensive action of captopril in the spontaneously hypertensive rat is associated with changes in body sodium, water and plasma aldosterone concentration. The alterations in brain angiotensin-converting enzyme activity following captopril treatment suggest that, with chronic administration, captopril can alter the activity of the brain renin-angiotensin system.

Notes: This study was designed to compare the activity of three structurally different drugs (SQ 14 225, SA 446, and MK 421) as inhibitors of angiotensin converting enzyme in vivo and to compare their effects in two experimental models of hypertension.2 MK 421 was less effective than SA 446 or SQ 14 225 in suppressing the pressor responses to intravenous angiotensin I 3 min after the administration of low doses of the converting enzyme inhibitors (CEIs) but more effective than SA 446 or SQ 14 225 30 min or longer after doses of CEIs ranging from 25 to 2500 nmol/kg i.v.3 The CEIs administered at 8 μmol/kg intravenously blocked the pressor response to angiotensin I (AI) to a similar maximal effect but the time for recovery was much slower for MK 421 than for SQ 14 225 or SA 446. After oral administration (15 mg/kg) prolonged blockade was observed with each of the three drugs although some recovery occurred with SA 446 after 5 h. The effect of a small dose of MK 421 intravenously (0.4 μmol/kg) was more prolonged in anaesthetized than in conscious spontaneously hypertensive rats (SHR).4 Anaesthetized adult SHR showed slow progressive falls of blood pressure after 8 /unol/kg of each drug intravenously although the effect of SA 446 was less than for SQ 14 225 or MK 421 which were equipotent. After acute oral administration of each CEI at 80 μmol/kg, conscious SHR showed significant falls in blood pressure but the effect of SA 446 was less than the other two inhibitors which appeared equipotent.6 After chronic oral administration of the drugs to conscious SHR, SA 446 (80 μmol/kg per day) did not alter blood pressure although SQ 14 225 was effective at this dose. At a higher dose of 160 /μmol/kg per day SA 446 significantly lowered blood pressure of SHR in a manner similar to the same dose of SQ 14 225 or MK 421.7. We conclude that the three drugs are potent, orally effective converting enzyme inhibitors. The duration of action was in the order MK 421 〉SQ 14 225 〉SA 446. MK 421 appears the most potent due to both a higher affinity for converting enzyme in vitro and a longer persistence of action in vivo. In renal hypertension, the drugs appeared equipotent but in the SHR at low doses, SA 446 was ineffective.

Notes: 1. An examination was made of the effect of prenatal, high salt (5% w/w) and low salt (0.1% w/w) diet on the blood pressure and ability to excrete a salt load of mature spontaneously hypertensive rats (SHR) of the Okamoto strain maintained on normal salt (0.8% w/w) diet after weaning.2. Prenatal high salt diet resulted in a significant exacerbation of the hypertension of 4 month old SHR when compared with animals given prenatal low salt diet.3. Three month old SHR given prenatal, high salt diet exhibited a significantly reduced Na+ excretion following a single, oral salt load (150 mmol/l, 1% bodyweight) when compared with the low salt group.4. Thus, prenatal, high salt diet may influence body fluid homeostasis in genetically susceptible individuals later in life.

Notes: 1. DOCA and 9α-fludrocortisone were given to rats.2. Plasma renin fell rapidly with both treatments.3. Renal renin fell slowly to a low level.4. Renal renin fell to a lower level with DOCA than with 9α-fludrocortisone.5. When DOCA and 9α-fludrocortisone were stopped plasma renin levels rose rapidly and the renal renin levels increased.6. The data suggest that synthesis is altered rapidly but it takes a prolonged time for the kidney to become depleted of renin due to the high tissue stores and the associated inhibition of release.