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Biomedical subjects

L Tobian

Publications and source records attributed to L Tobian.

At least 37 records · Page 2Linked to original sources
PubMed1990

Dietary K determines NaCl sensitivity in NaCl-induced rises of blood pressure in spontaneously hypertensive rats.

The current study tested whether the spontaneously hypertensive rats (SHR) from Charles River Laboratories are resistant or not to NaCl-induced rises of blood pressure and stroke deaths. These rats are fairly NaCl-resistant on a 2.1% high K diet, whereas they are quite susceptible to NaCl-induced hypertension and stroke deaths on a 0.5% normal K diet. Thus, a high K diet strongly protects against an NaCl-induced rise of blood pressure as well as stroke deaths in these SHR rats. Hence the level of dietary K determines the degree of NaCl sensitivity in these SHR rats.

Animals↗
PubMed1990

High sodium chloride diets injure arteries and raise mortality without changing blood pressure.

High NaCl diets often increase blood pressure and thereby accelerate lesions in arterial walls. Could high NaCl diets increase arterial lesions without raising blood pressure? To test this, 100 uninephrectomized Dahl salt-resistant (DR) rats (highly resistant to NaCl hypertension) were administered deoxycorticosterone acetate (DOCA) (250 mg/kg) in silicone implants and drinking water containing 1% NaCl for 6 weeks. Then the DOCA and saline were removed, and the rats were allowed to recover for 4 weeks. Intra-arterial mean blood pressures on all rats allowed division of the rats into two matched groups, each group with an average blood pressure of 160 mm Hg. One group continued on a 0.3% NaCl diet, whereas the other group began an 8% NaCl diet for 8 weeks. After 5 weeks on these two diets, the intra-arterial blood pressure averaged 158 mm Hg in both groups. Thus, the 8% NaCl diet produced no further increase in blood pressure in the DR rats. Nevertheless, after 8 weeks on the 8% NaCl diet, 53% of the rats (26 of 49) had died; whereas in the group on the 0.3% NaCl diet, not one rat (0 of 51) had died (p less than 0.000001). After 7 more weeks on the 8% NaCl diet, all the rats in this group had died.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Deleterious effects of high magnesium diets and beneficial effects of high potassium diets in hypertensive stroke-prone rats.

The effect of varying amounts of dietary magnesium (Mg) in conjunction with potassium (K) on hypertension and stroke mortality in hypertensive stroke-prone (SHRsp) rats was studied. These results show that high K (2.1%) diets strongly protect against stroke mortality and rises of blood pressure, while high Mg (0.26%) diets appeared to increase stroke mortality and accelerate the rise of blood pressure in SHRsp rats. Similarly, medium high (1.3%) levels of K in the diet significantly reduced blood pressure and stroke mortality but not nearly as much as the 2.1% K in the high K diet.

Animals↗
PubMed1989

Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat.

Renal distribution of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, an 18% reduction (p less than .025). Second study: Male Sprague-Dawley rats were made prostaglandin deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin deficient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p less than .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.

Animals↗
PubMed1989

High magnesium diets increase blood pressure and enhance stroke mortality in hypertensive SHRsp rats.

The effect of varying amounts of dietary magnesium in conjunction with potassium (K) on hypertension and stroke mortality in hypertensive stroke prone (SHRsp) rats was studied. These results show that high K (2.1%) diets strongly protect against stroke mortality and rises of blood pressure, while high magnesium (Mg) (0.26%) diets appeared to increase stroke mortality and accelerate the rise of blood pressure in SHRsp rats. Similarly, medium-high (1.3%) levels of K in the diet significantly reduced blood pressure and stroke mortality but not nearly as much as the 2.1% K in the high K diet.

Animals↗
PubMed1989

A glomerular defect in prehypertensive Dahl S rats, which limits their capacity to increase GFR.

There is a great need to discover traits that predict future human hypertension. Our previous studies found abnormal glomerular filtration rates (GFRs) in isolated kidneys of Dahl S rats. Such GFR alterations were sought in intact, low NaCl, prehypertensive Dahl S rats. Such Dahl S rats are genetically susceptible to NaCl hypertension but are normotensive on low NaCl. On .3% low NaCl, BP of 12 Dahl S rats averaged 138 mm Hg v 131 in 12 Dahl R rats (NS). Glomerular filtration rates under inactin anesthesia were measured during two 20-minute periods before a 20-minute amino acid infusion and also during three 20-minute periods after the amino acid infusion. Before the amino acid infusion, GFRs averaged 3.3 mL/min in S rats v 3.25 in R rats (NS). After the amino acid infusion, R rats showed a progressive rise in GFR: 4.7, 5.1 and 5.4 in three successive 20-minute periods. In these same three periods after amino acids, the S rats had GFRs of 3.8, 3.8, and 3.8. Thus R rats had an 81% increase of GFR after amino acids, whereas S rats increased only 18%, a 78% lower increase, P less than .001. The R rats had the normal rise of GFR in response to an amino acid load. Prehypertensive S rats had virtually no increase in GFR after the amino acid infusion. Even though both S & R rats had BPs well within the normal range, the ability to increase GFR after amino acid infusion was markedly impaired in prehypertensive S rats. This defect could possibly be used to predict future hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1989

Atherosclerotic cholesterol ester deposition is markedly reduced with a high-potassium diet.

In a normal rat on a normal diet, no cholesterol esters are detected in the aorta by gas chromatography. Stroke-prone spontaneously hypertensive rats (SHR) were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats ingested a normal (0.5%) level of potassium in the diet. Another group of 10 rats ingested a high (2.1%) potassium level. Mean intra-arterial blood pressures averaged 165 mmHg in the normal-potassium group and 161 mmHg in the high-potassium group (NS). Serum cholesterol levels averaged 229 mg/dl in the normal-potassium group and 214 mg/dl in the high-potassium group (NS). Total aortic cholesterol esters per rat involving 16- and 18-carbon chain fatty acids averaged 187 micrograms in normal-potassium rats versus 68 micrograms in high-potassium rats. These were the main esters; other esters were negligible. Thus, the high-potassium diet reduced cholesterol ester deposits by 64% (P less than 0.0003), even though blood pressures and cholesterol levels were quite similar in the two groups. Both high cholesterol and high blood pressure injure endothelial cells and increase the invasion of macrophages and vascular smooth muscle cells into the intima; they also increase endothelial permeability to proteins. With high plasma cholesterol levels, these processes lead to atherosclerosis with cholesterol ester deposition. The high-potassium diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could be useful for preventing heart attacks and sudden coronary death in human hypertension.

Animals↗
PubMed1989

How is the NaCl signal transmitted in NaCl-induced hypertension?

Is the NaCl signal perceived as a small increase in the concentration of NaCl in extracellular fluid? We used 8 g NaCl/100 g soluble nutrients and fed only a hypertonic (1.4% NaCl) or a hypotonic (0.45% NaCl) drink to Dahl salt-sensitive (DS) rats. After 12 weeks, 11 rats receiving the hypertonic drink had a mean blood pressure of 195 mm Hg versus 195 mm Hg in 12 rats receiving the hypotonic drink. Thus, the high-NaCl signal seems unrelated to a higher NaCl concentration in extracellular fluid, thereby suggesting volume signals. Most volume controls are near the third brain ventricle (3V). As a working hypothesis, high dietary NaCl may swell the tissues surrounding 3V, which is slitlike. Such swelling would partially close the upper part of the slit and cause ependymal cells and nerve fibers on opposite walls to touch, possibly leading to hypertension in susceptible humans or rats. To test this, we stereotaxically blocked the aqueduct with inert silicone to produce hydrocephalus of 3V in DS rats and thus prevent ependymal cells and nerve fibers from touching. After blocking or sham-blocking the aqueduct, either a 6% NaCl diet or a 0.23% NaCl diet was started. Intra-arterial blood pressure was taken after 6 weeks. A group of 28 sham-blocked rats and a group of 29 blocked rats, all fed a 0.23% low NaCl diet, had equal blood pressures averaging 130 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Hypothesis: low dietary K may lead to renal failure in blacks with hypertension and severe intimal thickening.

Hypertension can precipitate renal failure in blacks. The key hypertensive lesion in the renal vasculature is severe intimal thickening in interlobular arteries without fibrinoid necrosis. Hypertensive endothelial injury is the likely cause of the intimal thickening. High K diets prevent wall thickening of small renal arteries and arterioles in hypertensive Dahl S rats and greatly reduce both medial and intimal thickening of the aorta and mesenteric and carotid arteries in hypertensive stroke-prone SHRsp rats. In view of this, it is likely that the low K diet characteristically consumed by blacks exaggerates their hypertensive intimal thickening. A high K diet could possibly preserve these arteries and avert much renal failure.

Animals↗
PubMed1988

The Volhard lecture. Potassium and sodium in hypertension.

For the first 98.5% of mankind's existence, prehistoric people all ate low-sodium high-potassium, low-fat diets. With evolutionary forces working all this while, humans became very well adapted to the low-sodium, high-potassium, low-fat diet. In modern times, man has deserted his ancient cuisine and now favours a high-sodium, low-potassium, high-fat diet, which has produced several 'diseases of civilization', including hypertension. Many studies indicate that a 'normal'-potassium diet encourages arterial thickening and lesions in hypertensive arteries and kidneys, whereas a high-potassium diet can prevent many of these arterial and renal lesions, even though the blood pressure remains equally hypertensive. The high-potassium diet also tends to retard the development of hypertension. In susceptible people and rats, a high-NaCl diet leads to hypertension. This susceptibility is probably brought about by kidneys that have a sluggish sodium excretion in response to a NaCl load. This type of kidney combined with a high-NaCl diet tends to produce NaCl retention. Evidence is presented that this NaCl signal may be perceived by structures in the wall of the third brain ventricle. In susceptible men or rats, this can lead to a hypertensive rise in blood pressure, which over time can become partially irreversible, even though a low-NaCl diet is reinstituted.

Animals↗
PubMed1988

High potassium diets protect against dysfunction of endothelial cells in stroke-prone spontaneously hypertensive rats.

Two lines of evidence strongly support the hypothesis that high potassium diets protect arterial endothelial cells from hypertensive damage. Stroke-prone spontaneously hypertensive rats (SHRSP) fed normal (0.75%) K or high (2.1%) K and normotensive Wistar-Kyoto rats (WKY) were examined in an endothelial function study and a histological study. In the endothelial function study, aortic rings were suspended in tissue baths to monitor isometric tension. Rings contracted with norepinephrine were tested with acetylcholine and sodium nitroprusside. In normal K SHRSP (blood pressure, 156 mm Hg), endothelium-dependent acetylcholine relaxation was severely depressed by 49% (p less than 0.001), whereas in high K SHRSP (blood pressure, 155 mm Hg), normal values were preserved. Endothelium-independent nitroprusside relaxation was virtually the same in both the SHRSP groups (high K vs normal K diet). Since indomethacin did not improve the impaired acetylcholine relaxation in normal K SHRSP, the cyclooxygenase products do not appear to have affected the endothelium-dependent relaxation in the normal K SHRSP. Thus, the endothelium-dependent relaxation response was much decreased in the normal K SHRSP and was preserved in the high K SHRSP. Thus, a high K diet appears to protect the aortic endothelium from a hypertension-induced dysfunction. In the histological study, aortic and mesenteric intimal lesions were assessed blindly under the microscope and graded from 0 to 60 for aortic and from 0 to 40 for mesenteric lesions. Aortic intimal lesion scores were 28 in normal K SHRSP (blood pressure, 209 mm Hg) and 13 in high K SHRSP (blood pressure, 207 mm Hg; -54%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Prehypertensive Dahl S rats show no rise in glomerular filtration rate after an amino acid infusion.

When one administers a protein or amino acid load, both GFR and renal blood flow increase about 40% in normal humans as well as in dogs and rats. The protein load causes vasodilation in both the afferent and the efferent arterioles. In these prehypertensive Dahl S rats, it is likely that there is already some vasodilation of the afferent and efferent arterioles and possibly some mesangial relaxation, in order to bring the GFR to normal levels in the face of some intrinsic abnormality in glomerular filtration. Since these arterioles are already dilated, there can be little further dilation in response to the amino acid load and hence no further increase in GFR. It is possible that this limited capacity for further vasodilation could serve as a predictor of future hypertension.

Amino Acids↗
PubMed1987

Does essential hypertension lead to renal failure?

Systemic hypertension can lead to renal failure in blacks. The key lesion is severe intimal thickening in interlobular arteries without fibrinoid necrosis. Hypertensive endothelial injury is the likely root cause of the intimal thickening. High potassium diets prevent wall thickening of small renal arteries and arterioles in hypertensive Dahl S rats and also greatly reduce both medial and intimal thickening of the aorta and mesenteric and carotid arteries in spontaneously hypertensive stroke-prone rats. In view of this, it is quite likely that the low potassium diet characteristically seen in blacks exaggerates the hypertensive intimal thickening. A high potassium diet could possibly preserve these arteries and avert much renal failure.

Animals↗
PubMed1987

Alterations of vascular prostacyclin and thromboxane A2 in Dahl genetical strain susceptible to salt-induced hypertension.

To assess the implications of vascular eicosanoids system in the hypertension of Dahl salt-sensitive (Dahl S) strain, we investigated the production of vascular vasodepressor and vasoconstrictor eicosanoids in Dahl S rats. 14-week-old Dahl S rats on a 0.11% NaCl diet (normotension) or a 0.3% NaCl diet (borderline hypertension) had a significantly lowered generation of vascular prostacyclin (PGI2), compared with Dahl salt-resistant (Dahl R) rats. The impairment of vascular PGI2 in Dahl S rats was restored to the normal level of Dahl R rats with the elevation of blood pressure induced by a high salt diet (4% NaCl). The production of vascular PGI2 was closely related to the height of blood pressure. The deterioration of vascular PGI2 was also found in 4-week-old Dahl S rats with normotension. Conversely, vascular thromboxane A2 (TXA2) was significantly enhanced in 14-week-old Dahl S rats in all of the feeding groups. Thus, it seems possible that the proved alterations of the vasodepressor and vasoconstrictor eicosanoids partially contribute to the genesis of salt hypertension. Although the exact mechanisms remain obscure, the adaptation of vascular PGI2 on a high salt diet may be suitable to compete with the high blood pressure and to protect against the vascular damage.

Aging↗
PubMed1986

Perspectives on treating hypertension.

Lowering the blood pressure to levels for which the arterial system has been designed should reduce various complications in the coronary and cerebral arteries, the heart, and the kidney. However, the antihypertensive treatment itself should not produce any significant damage. It is very likely that early modes of antihypertensive treatment did cause some biologic harm, which prevented the expected reduction in the incidence of coronary artery disease. However, the inability of these early forms of treatment to greatly improve coronary artery disease does not necessarily apply to treatments of the future.

Adrenergic beta-Antagonists↗
PubMed1986

High potassium diets markedly protect against stroke deaths and kidney disease in hypertensive rats, a possible legacy from prehistoric times.

Male spontaneously hypertensive stroke-prone (SHRsp) rats were fed 4% NaCl diets containing either 0.75% (normal) K or 2.11% (high) K, starting at 6 weeks of age. After 8 months on these diets, 40 out of 58 SHRsp rats on the 0.75% K diet had died (69% mortality) versus 2 dead out of 95 on the 2.11% K diet (2% mortality), a 97% reduction in mortality, p less than 0.00001. After 20 weeks on the diets, the daytime and nighttime blood pressures of each rat were measured intraarterially under light ether anesthesia. Using these accurate blood pressures, we selected two groups precisely matched for blood pressure. One matched SHRsp group (BP 182) ate the 0.75% K diet and 30 out of 47 rats died (64% mortality). The other matched SHRsp group (BP 182) ate the 2.11% K diet and 2 out of 35 died (6% mortality), a 91% reduction of mortality, p less than 0.0001. Seemingly, this striking reduction in mortality rate with the 2.11% high K diet does not depend on a lowering of blood pressure. High K diets do not change body Na or K. Dry weight of mesenteric arterioles was reduced 29% on the 2.11% K diet versus the 0.75% K diet (5.43 vs. 7.66 mg) (p less than 0.0001), indicating a greatly reduced hypertensive hypertrophy. In nine surviving SHRsp rats on the 0.75% K diet, 13 of 36 brain hemisphere slides (4 slides per rat) showed infarcts (36%). In 11 surviving SHRsp rats on the 2.11% K diet, 1 of 44 brain slides showed infarcts (2%), a 94.5% reduction, p less than 0.0001.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗