Story of the birth of the journal called Hypertension.
Explore the source record for details and available documents.
American Heart Association↗
Biomedical subjects
L Tobian
Publications and source records attributed to L Tobian.
Introduction to the Dahl symposium.
Explore the source record for details and available documents.
Animals↗
Dietary sodium chloride and potassium have effects on the pathophysiology of hypertension in humans and animals.
A diet high in NaCl can raise blood pressure in susceptible people and animals, probably by similar mechanisms. The possibly harmful effects of a high-NaCl diet are not unexpected because both prehistoric humans and mammals evolved in a low-NaCl environment. Evolutionary forces molded mammals to adapt well to a low sodium intake; modern high NaCl intakes go against this adaptation. A high-NaCl diet can cause premature mortality by raising blood pressure in susceptible people. We have new evidence that in hypertension, a high-NaCl diet can cause a great increase in mortality even though it does not cause a further blood pressure rise, partially because of multiple small cerebral infarcts. 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 blood pressure rise. The combination of a tendency by the kidneys to retain NaCl together with a high NaCl intake can produce a blood pressure rise. This combination tends to cause NaCl retention, which can trigger blood pressure rises in susceptible humans and animals. Such blood pressure rises can augment renal NaCl excretion and regain the previous NaCl balance. In Dahl salt-sensitive rats several renal abnormalities encourage sodium retention. By analogy, renal "abnormalities" are probably present in people susceptible to hypertension.
Animals↗
Introduction to the symposium: the sympathetic nervous system really is a key element in hypertension, with treatment implications.
Explore the source record for details and available documents.
Animals↗
High potassium diets reduce endothelial permeability in stroke-prone spontaneously hypertensive rats.
1. High potassium (K) diets are known to prevent hypertensive arterial lesions and reduce stroke incidence without affecting blood pressure. 2. To elucidate the mechanism of this beneficial effect, we studied the effect of K supplementation on the extravasation of plasma albumin in high NaCl-fed stroke-prone spontaneously hypertensive rats (SHRSP). Increased permeability of the endothelium to macromolecules is assumed to be an early manifestation of vascular injury. 3. The disappearance of intravenously injected [125I]-albumin was examined in SHRSP rats fed high NaCl diets containing either 0.5% normal K or 2.1% high K for 5 weeks. 4. The bodyweight, blood pressure, plasma volume and urinary protein excretion were not significantly different between the two SHRSP groups. 5. The high K SHRSP showed a slower plasma albumin disappearance rate than the normal K SHRSP (10.3 vs 14.7%/h, P < 0.004). The albumin radioactivity remaining in the aortic wall and in the brain after removing blood after perfusion was lower in the high K SHRSP than in the normal K SHRSP (aorta, -20%, P < 0.02; brain, -26%, P < 0.04). 6. These results suggest that the high K diet reduced the endothelial permeability to albumin in high NaCl-fed SHRSP rats. High K diets may have a protective effect against endothelial dysfunction and thereby contribute to the reduction of vascular lesion formation and stroke incidence.
Animals↗
Hypertension from carotid occlusion decreases renal papillary plasma flow, hypotension from hemorrhage increases it, an autoregulatory paradox.
Renal papillary plasma flow was tested during acute increases and decreases of perfusion pressure using the 125I-labelled albumin technique. Increases of pressure were attained through ligation of carotid arteries; decreases of pressure through modest hemorrhage. In 12 control rats with blood pressure of 144 mmHg, the papillary plasma flow averaged 21.5 ml per 100 g papilla per min. In 12 rats after ligation of carotid arteries, blood pressure rose from 143 mmHg to 172, a 20% increase. The papillary plasma flow in these rats with acute hypertension averaged 17.9 ml per 100 g papilla per min, a 17% decrease (p < 0.025). In another 12 rats after bleeding 1% of body weight over a period of 10 min, blood pressure dropped from 146 mmHg to 104, a 29% decrease. The papillary plasma flow in these rats with acute hypotension averaged 26.0 ml per 100g papilla per min, a 21% increase (p < 0.025). The decrease in papillary plasma flow during acute hypertension strongly suggests an increased vascular resistance of the descending vasa recta, while the increase in papillary plasma flow during acute hypotension suggests that vasodilatation occurred in these vessels. This dilatation may be produced by the local release of prostaglandins or other vasoactive substances. Thus, the renal papilla appears to "overshoot" its autoregulation of plasma flow, with actual reduced flow during an acute blood pressure rise and increased flow during an acute blood pressure fall, an enigmatic over-compensation.
Animals↗
High potassium diets reduce vascular and plasma lipid peroxides in stroke-prone spontaneously hypertensive rats.
We examined the effect of high potassium (K) diet on oxidative stress to endothelium in hypertensive rats. Five-week-old stroke-prone spontaneously hypertensive rats (SHRsp) were fed a 5% high NaCl diet containing either 0.5% normal K (n = 28) or 2.1% high K (n = 19) for 6 weeks, and lipid peroxides in the aortic intima and plasma were measured. Lipid peroxides were extracted into an organic solvent to avoid the interference of carbohydrates or glycoproteins, and malondialdehyde (MDA) produced from lipid peroxides by acid-heating was measured by its reaction to thiobarbituric acid. The antioxidant butylated hydroxytoluene prevented spurious lipid peroxide formation during the whole procedure, and optimum Fe3+ allowed a maximum MDA production from lipid peroxides. The high K SHRsp showed lower lipid peroxide levels than the normal K SHRsp both in the intima (5.6 +/- 0.3 vs. 7.2 +/- 0.4 nmol MDA/mg fatty acids, p < 0.003) and plasma (0.91 +/- 0.08 vs. 1.46 +/- 0.10 nmol MDA/ml, p < 0.001). Mean arterial pressure was slightly lower by 13 mmHg in the high K SHRsp, but these differences were still obvious even when we compared groups of rats with precisely matching blood pressures. These results indicate that high K diets reduce oxidative stress on the endothelium of high NaCl-fed SHRsp independently of blood pressure changes. This effect may be involved in the mechanism by which high K diets protect endothelium and reduce stroke incidence in hypertensive animals. Thus, we improved the method of lipid peroxide measurement and propose the protective effects of high K diet against oxidative stress to endothelium in hypertension animals.
Animals↗
Effect of high potassium diets on the vascular and renal prostaglandin system in stroke-prone spontaneously hypertensive rats.
High potassium (K) diets are known to have a protective effect on the endothelium and the kidney against hypertensive injury independent of blood pressure change. Vasodepressor prostaglandins (PGs) have been shown to be cytoprotective in various tissues. This study investigated the effect of high K diets on the vascular and renal eicosanoid system in stroke-prone spontaneously hypertensive rats (SHRsp). Eicosanoid production by the aorta and eicosanoid content in the renal cortex were examined in SHRsp rats fed high NaCl diets containing either 0.5% K (normal) or 2.1% K (high). Although the high K diet did not affect the blood pressure, SHRsp on the high K diet had less thickening of the aortic wall than SHRsp on the normal K diet (-15%, p < 0.001). The aortic strip of the high K SHRsp produced less vasodepressor PG than that of the normal K SHRsp when they were incubated in a medium (PGI2 -45%, p < 0.003; PGE2 -34%, p < 0.001). Furthermore, when the aorta was perfused in a chamber at hypertensive pressure, again the high K aorta showed reduced PGI2 production as compared with the normal K aorta (intravascular side -52%, p < 0.01). Eicosanoid content in the renal cortex was not significantly different between the normal K and the high K SHRsp (PGI2 79 vs 87 ng/g dry weight; PGE2 214 vs 233 ng/g dry weight). Thus, the high K diet reduced vascular eicosanoid production but did not alter eicosanoid content in the renal cortex. The reduced vascular eicosanoid production in the high K SHRsp may reflect the reduced necessity for cytoprotective vasodepressor PG against vascular injuries.
Administration, Oral↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
High-potassium diets greatly increase the release of growth-inhibiting agents from aortae of stroke-prone spontaneously hypertensive rats, thereby partially explaining reduced aortic wall thickening.
Explore the source record for details and available documents.
Animals↗
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↗