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Biomedical subjects

L Tobian

Publications and source records attributed to L Tobian.

At least 19 recordsLinked to original sources
PubMed1994

Modern strategies to prevent coronary sequelae and stroke in hypertensive patients differ from the JNC V Consensus Guidelines.

In recent years, government agencies of many countries have established consensus guidelines for the evaluation and treatment of hypertension. Once published, guidelines tend to be perceived as directives by a variety of health care providers. Unfortunately, these guidelines often do not reflect the practices of most hypertension experts. This report summarizes the opinions of seven hypertension experts concerning the impact of "official" guidelines on clinical practice. In addition, the individual therapeutic recommendations of these panel members are summarized. Their different treatment strategies reflect the diversity of first rate treatment plans that aim to reduce the cardiovascular sequelae in individual patients with essential hypertension. Most importantly, not one of these seven treatment strategies followed the "preferred" treatment of the U.S. guidelines, which recommend diuretics and beta-blockers as first-line therapy. The present authors approach the treatment of hypertension as a means to reduce cardiovascular events. Thus, reduction of blood pressure is not the most important therapeutic endpoint. The panel believes that whereas many different drugs can produce effective blood pressure reduction, the modern primary goal of antihypertensive drug therapy is to select a regimen most likely to prolong the quality and duration of life. In real terms, this means that the primary goal of treatment is the prevention of the major vascular sequelae of hypertension (heart attack, ventricular remodeling, hypertrophy, heart failure, and stroke) that shorten useful life. There are a number of effective hypertensive treatments, which can be selected based on individual patient requirements. However, many consensus guidelines do not allow the flexibility required to optimize individual patient treatment. As a result, health care providers should not feel compelled to regard the preferences of "official" guidelines as the best, modern, state-of-the-art therapy for an individual patient. All seven experts who are deeply involved in the daily care of patients preferred drugs other than beta-blockers and diuretics (the Joint National Committee [JNC] choices) for first-line therapy of hypertension.

Cardiovascular Diseases↗
PubMed1992

High potassium diets greatly increase growth-inhibiting agents in aortas of hypertensive rats.

High potassium diets greatly reduce intimal and medial thickening in stroke-prone spontaneously hypertensive rats (SHRSP). In vascular smooth muscle cells, transforming growth factor-beta (TGF-beta) inhibits proliferation. To test whether high potassium diets decrease aortic thickening through TGF-beta, we measured TGF-beta-like activity in medium bathing aortas from rats fed either normal potassium or high potassium diets. Five-week-old SHRSP were fed 6% high NaCl diets containing either normal (0.5%) potassium (11 rats) or high (2.1%) potassium (14 rats) for 7 weeks. Aortas were freshly excised and perfused for 3 hours with tissue culture medium at ordinary arterial pressures. TGF-beta-like activity in the acid-activated perfusing medium was assessed using the growth inhibitory action on mink lung cells. Growth inhibition was assessed by [3H]thymidine incorporation. In the medium perfusing the outside of the aorta, the growth inhibitory rates were 2.5 times higher in high potassium SHRSP than in normal potassium SHRSP (-49% versus -20%, p less than 0.03). Antibodies to TGF-beta 1 and TGF-beta 2 were added to other aliquots and did not alter the results whatsoever. Thus, the difference in growth inhibition was not due to differences in TGF-beta. The high potassium aortas released 2.5 times more growth-inhibiting agents than the normal potassium aortas. The same pattern of growth inhibition was also seen using vascular smooth muscle cells rather than mink lung cells (r = +0.818, p less than 0.001, n = 13). The increased growth inhibition of high potassium aortas was not due to an increased release of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Protecting arteries against hypertensive injury.

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 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. The use of the high K diet is a prime example of protecting arteries in a hypertensive setting. This is the new dimension in hypertension therapy, protecting the arteries in addition to normalizing the blood pressure.

Animals↗
PubMed1991

Newborn cardiorenal dynamics: a state of atrial natriuretic peptide unresponsiveness.

The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion were significantly different (P = 0.017). We speculate that ANF unresponsiveness in the 1-day-old lamb is related to physiological transitions during the birth process and that the maturation of the renal response to VE may require maturation of the atrial mechanism which permits ANF secretion.

Aging↗
PubMed1991

Salt and hypertension. Lessons from animal models that relate to human hypertension.

A high NaCl diet can raise blood pressure in both susceptible people and in susceptible animals, and the mechanisms are probably quite similar for both humans and animals. The possibly harmful effects of a high NaCl diet are not unexpected since both prehistoric man and mammals evolved in a low NaCl world. Evolutionary forces molded mammals to adapt well to a low sodium intake; the modern high NaCl intake goes "against the grain" of this adaptation. The high NaCl diet can cause premature mortality by raising blood pressure in susceptible people. We have new evidence that in a hypertensive setting, a high NaCl diet can increase mortality even though it does not cause a further rise of blood pressure. Multiple small cerebral infarcts are a partial cause of this excess mortality. Recent evidence also indicates that a high potassium diet reduces the rise of blood pressure caused by a high NaCl diet, whereas a low normal potassium intake encourages an NaCl-induced rise of blood pressure. It is the combination of kidneys that tends to retain NaCl together with a high NaCl intake that produces a rise in blood pressure. This combination tends to cause NaCl retention, which can trigger a rise in blood pressure in susceptible humans and animals. Such a rise in blood pressure can augment renal NaCl excretion and regain the previous NaCl balance. In the Dahl salt-sensitive (DS) rat, there are several renal abnormalities that would tend to encourage sodium retention. By analogy, renal "abnormalities" are probably present in people susceptible to hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Aqueduct block markedly reduces mortality and hypertension in post-deoxycorticosterone acetate Dahl salt-resistant rats.

When Dahl salt-resistant (DR) rats are given mild post-deoxycorticosterone acetate (DOCA) hypertension, they will have, within 8 weeks, a 53% mortality on a high NaCl diet, without a rise of blood pressure. Forty-two DR rats were given DOCA in silicone (250 mg/kg) and 1% NaCl to drink. After 4 weeks, the DOCA and 1% saline were removed and replaced with a low NaCl diet and tap water. One week later, they were divided into two groups perfectly matched for blood pressure (154 mm Hg). One group had the aqueduct of Sylvius blocked with silicone and epoxy materials; the other group had a sham block. After 4 more recovery weeks on a low NaCl diet, blood pressure averaged 171 mm Hg in sham rats and 147 mm Hg in truly blocked rats (p less than 0.0001). Thus, the aqueduct block prevented most of the post-DOCA hypertension and permitted a strong post-DOCA recovery from the acute DOCA hypertension. The rats with the sham block had an actual rise in blood pressure during the post-DOCA recovery period. The vicious cycle leading to permanent post-DOCA NaCl hypertension was broken by the aqueduct block. Then both groups began an 8% high NaCl diet, and after 4 weeks, blood pressure averaged 184 mm Hg in sham and 155 mm Hg in truly blocked rats (p less than 0.0001). After 12 weeks on 8% NaCl, all sham rats had died (28 of 28), whereas only one of 14 truly blocked rats had died (93% reduction in mortality, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1991

In SHR rats, dietary potassium determines NaCl sensitivity in NaCl-induced rises of blood pressure.

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 deaths. These rats are fairly NaCl-resistant on a 2.1% high K diet, whereas they are quite susceptible to NaCl-induced hypertension and deaths on a 0.5% normal K diet. Thus, a high K diet strongly protects against a NaCl-induced rise of blood pressure as well as deaths in these SHR rats. Hence the level of dietary K determines the degree of NaCl sensitivity in these SHR rats.

Animals↗
PubMed1991

Cholesterol ester deposition is reduced in rats with hypercholesterolemia and hypertension.

High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. We investigated whether a high K diet would influence cholesterol ester deposits in stroke prone SHR rats. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intra-arterial BPs averaged 165 mmHg in the normal K group and 161 mmHg in the high K group (NS). The serum cholesterol averaged 229 mg/dl in the normal K group and 214 in the high K group (NS). Total aortic cholesterol esters per rat averaged 187 micrograms in normal K vs 68 micrograms in high K, measured by gas chromatography. Thus high K reduced cholesterol ester deposits by 64% (p less than .0003), even though BPs and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of monocytes and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possibly be useful for preventing heart attacks in human hypertension.

Animals↗
PubMed1990

High K diets markedly reduce atherosclerotic cholesterol ester deposition in aortas of rats with hypercholesterolemia and hypertension.

High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. Would a high K diet influence cholesterol ester deposits? In a normal rat on a normal diet, no cholesterol esters are detected in the aorta. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intraarterial blood pressures averaged 165 mm Hg in the normal K group and 161 mm Hg in the high K group (P = NS). The serum cholesterol averaged 229 mg/dL in the normal K group and 214 in the high K group (P = NS). Total aortic cholesterol esters per rat involving 16 and 18 carbon chain fatty acids averaged 187 micrograms in normal K v 68 micrograms in high K, measured by gas chromatography. These were the main esters; other esters were negligible. Thus high K reduced cholesterol ester deposits by 64% (P less than .0003), even though blood pressure and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of macrophages and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possible be useful for preventing atherosclerotic complications such as heart attacks in human hypertension.

Animals↗
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↗