bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular response in black and white hypertensives.
Authors: Rowlands D B , De Giovanni J , McLeay R A , Watson R D , Stallard T J , Littler W A
Published: June 2012

Sixteen untreated black patients with mild-to-moderate hypertension and no evidence of target organ damage were matched for age, sex, casual blood pressure (BP), and socioeconomic status with 16 white hypertensives. All patients were studied under standardized conditions in the hospital where they underwent continuous intraarterial ambulatory monitoring of BP and assessment of BP control mechanisms. BP characteristics over prolonged periods of recording were similar for both groups, as were sinoaortic baroreflex activity and pressor response to isometric and dynamic exercise and to cold. Fasting cholesterol and triglyceride levels in both groups were similar. Resting plasma renin activity (PRA) was significantly lower in blacks, but no difference was observed in resting plasma norepinephrine levels. Urinary excretion of NA+ and K+ was also similar in both groups. Thus, results showed that casual BPs matched for black and whites, and recorded over a prolonged period, were similar in pattern, variability, and response to pressor stimuli. It appears that, if BP contributes to the different patterns of morbidity in blacks and whites, it is more likely to be the actual level of BP rather than differences in BP characteristics.
Catecholamines in discrete kidney regions. Changes in salt-sensitive Dahl hypertensive rats.
Authors: Fernandez-Pardal J , Saavedra J M
Published: June 2012

Steady state levels of catecholamines (dopamine, norepinephrine, and epinephrine) were measured by the use of radioenzymatic techniques in discrete areas of the kidney (outer and inner cortex, outer and inner medulla) dissected by a "punch" technique from frozen kidney sections of salt-sensitive (DS) and salt-resistant (DR) Dahl rats fed a low or high salt diet. All three catecholamines were present in all areas of the kidney examined. There were gradients of concentrations of each catecholamine in different kidney areas. Renal medullary areas contained proportionally more dopamine than cortical areas. The proportion of epinephrine with respect to the total catecholamine content was relatively high in the inner medulla. Genetic factors and the amount of dietary salt influenced the catecholamine content in specific kidney areas, and these changes were different according to the area considered. DS rats when fed a high salt diet presented increased systolic blood pressure but no increased levels of dopamine in the inner medulla nor of norepinephrine in the outer medulla and outer cortex. Results suggest that either the uptake, release, storage, synthesis, or catabolism of kidney catecholamines is altered in Dahl salt-sensitive (DS) hypertensive rats and suggest specific roles for each catecholamine in discrete areas of the kidney.
Heart size in inbred strains of rats. Part 2. Cardiovascular DNA and RNA contents during the development of cardiac enlargement in rats.
Authors: Tanase H , Yamori Y , Hansen C T , Lovenberg W
Published: June 2012

Enlargement and nucleic acid content of the cardiovascular system of several strains (SHRSP/N, SHR/N, OM/N, M520/N) of rats were compared with the WKY/N strain in an attempt to characterize cardiac enlargement. Cardiac enlargement in rats can be due to either hypertrophy (increase in myocyte size), hyperplasia (increase in cell number including supporting tissue), or a combination of both. The sum of the indices of the degree of hypertrophy and hyperplasia calculated from the difference of the heart and aorta deoxyribonucleic acid (DNA) concentration and total DNA content between each strain and the WKY/N was almost equal to the degree of heart and aorta enlargement. The SHRSP/N revealed a striking hypertrophy of myocardial cells from the prehypertensive stage, and hyperplasia appeared gradually with the elevation of blood pressure. In contrast, the SHR/N developed a marked hyperplasia with some hypertrophy at the prehypertensive stage. Cardiac enlargement of the OM/N was attributed to both hypertrophy and hyperplasia. A large heart weight of the M520/N was recognized at only a young age, and was due almost entirely to hyperplasia. Aortic enlargements were related to hyperplasia. An increased ribonucleic acid (RNA) concentration was observed in both ventricles of the SHRSP/N, SHR/N, and M520/N rats at 4 weeks of age, and in all of the four strains at 16 weeks of age. A significantly higher RNA concentration was indicated in the aorta of three hypertensive strains of SHRSP/N, SHR/N, and OM/N at established hypertensive stage. These changes might be related to manifestations of genetic or other factors such as the effect of elevated blood pressure.
Renal alpha-adrenergic receptor abnormality in the spontaneously hypertensive rat.
Authors: Graham R M , Pettinger W A , Sagalowsky A , Brabson J , Gandler T
Published: June 2012

Activation of renal alpha-adrenergic receptors induces vasoconstriction, proximal tubular reabsorption of sodium, and inhibition of renal release. Excesses of these effects are present in varying degrees in animal models of, and in patients with, "essential" hypertension. Since essential hypertension is genetically determined, we sought abnormalities of renal alpha-adrenergic receptors in the Okamoto-Aoki strain of spontaneously hypertensive rats (sr-SHR) and their stroke-prone variant (sp-SHR). Total alpha-adrenergic receptor concentrations were determined by Scatchard analysis of [3H]dihydroergocryptine binding to a renal membrane fraction and were found to be increased (p less than 0.02) in male sr-SHR at 4, 16, and 32 weeks of age and in female sr-SHR at 16 weeks of age as compared to age- and sex-matched Wistar-Kyoto controls. They were also increased in 9-week-old sp-SHR renal membranes (p less than 0.005). Further studies revealed that this increase in renal alpha-adrenergic receptors was due entirely to an increase in alpha 2-receptors as measured by [3H]yohimbine binding rather than to an increase in alpha 1-receptors as quantitated by [3H]prazosin binding. No difference in binding affinities of the various radioligands could be demonstrated between any of the hypertensive and normotensive groups of rats. Plasma norepinephrine levels were elevated (p less than 0.01) in the 4-, 9- and 16-week-old SHR, but not in the 32-week-old hypertensive rats. Thus, high renal alpha 2-adrenergic receptor number is coupled with a significant increase in plasma norepinephrine concentrations during the development of hypertension in SHR. By mediating an enhanced receptor-coupled response, such as increased proximal tubular sodium reabsorption, this abnormality of renal alpha-adrenergic receptors may contribute to some or all of the pathophysiologic derangements leading to hypertension in SHR.
Central pressor action of neurotensin in conscious rats.
Authors: Sumners C , Phillips M I , Richards E M
Published: June 2012

The effects of neurotensin upon blood pressure in conscious rats were examined after intracerebroventricular (i.v.t.) or intravenous (i.v.) administration of this peptide. Whereas i.v. injected neurotensin (0.1-2.0 microgram/kg) was depressor, i.v.t. injected neurotensin (1 microgram and above) was pressor. Peripheral depressor responses could not be repeated in the same animal due to tachyphylaxis, but central pressor responses were repeatable without reduction in magnitude, showing that the two effects were separate entities. Thyrotropin-releasing hormone (TRH), which is reported to be a potent neurotensin antagonist, completely abolished the neurotensin depressor response, and attenuated the central pressor action. TRH did not alter the central pressor effect of another peptide, angiotensin II (AII). The potent AII receptor antagonist saralasin, while abolishing the central pressor effect of AII, was completely without effect upon the neurotensin-induced pressor response. These results indicate that i.v.t. injected neurotensin and AII stimulate a rise in blood pressure via different receptors. The alpha-adrenergic antagonists phentolamine, prazosin, or yohimbine (injected i.v.t.) involvement of the sympathetic nervous system in this response. These results are discussed in relation to the central pressor actions of other neuropeptides.
Electrolyte and water balance in young spontaneously hypertensive rats.
Authors: Beierwaltes W H , Arendshorst W J , Klemmer P J
Published: June 2012

In metabolic balance studies the intake and excretion of sodium, potassium, and water were measured in spontaneously hypertensive rats (SHRs) of the Okamoto-Aoki strain and age-matched Wistar Kyoto rats (WKYs) that were 3 through 13 weeks of age. While fed their usual chow, young SHRs exhibited differences in excretion as compared to WKYs consuming essentially equivalent amounts of food and water. Fractional sodium and water excretion (percent of amount ingested) by SHRs were significantly less during Weeks 4-6 and 6-7, respectively, due to lower rates of urinary excretion. Potassium excretion was less in SHRs at 4-5 weeks. These observations indicate that SHRs retain more urinary sodium, potassium, and water during an early phase of hypertension than normotensive, age-matched WKYs. After 8 weeks of age, fractional excretion of electrolytes and water did not differ appreciably between strains. In another group of rats, sodium intake was restricted and observations were made from 3 through 13 weeks of age. Although SHRs excreted slightly less sodium, cumulative sodium balance was similar weeks of age and reduced the magnitude of the hypertension in 10- through 13-week-old SHRs. At the latter age, arterial pressure was not as high in sodium-restricted SHR as in SHR on the standard sodium diet, but it was elevated above that in either WKY groups. Thus dietary sodium restriction retards the development, but does not prevent the hypertension in SHR.
Effects of angiotensin II on the cardiac responses to sympathetic nerve stimulation in dogs.
Authors: Furukawa Y , Scipione P , Levy M N
Published: June 2012

In anesthetized dogs with the left cardiac sympathetic nerves and both vagal nerves intact, angiotensin II (AII) induced a substantial, dose-dependent increase in arterial blood pressure and small increments in cardiac cycle length and ventricular contractile force. In dogs in which the cardiac sympathetic and vagal nerves had been interrupted, AII produced similar increases in blood pressure and larger increases in contractile force, but it decreased the cardiac cycle length. In both groups of dogs, AII augmented substantially the positive inotropic responses to sympathetic nerve stimulation, but it enhanced the positive chronotropic responses only slightly. However, AII did not appreciably prolong the cardiac responses to sympathetic nerve stimulation, nor did it alter significantly the cardiac responses to norepinephrine infusions. Hence, at the dosage levels used, AII probably did not inhibit the neuronal uptake of norepinephrine appreciably nor did it enhance the responsiveness of the cardiac effector sites to norepinephrine. Therefore, the potentiation of the cardiac responses to sympathetic nerve stimulation by AII in these experiments was probably achieved principally by facilitating norepinephrine release from the adrenergic nerve terminals in the heart.
Insulin reverses hypertension and hypothalamic depression in streptozotocin diabetic rats.
Authors: Sasaki S , Buńag R D
Published: June 2012

Daily subcutaneous injections of lente insulin reduced the hypertension and bradycardia which developed consistently in streptozotocin diabetic rats. Insulin-treated rats also became less hyperglycemic, drank less water, and gained weight faster than untreated diabetic controls. Behavioral and tachycardiac effects elicited by electrical stimulation of the ventromedial hypothalamus while the rats were awake were similar, but attendant pressor responses were larger in those that had been treated with insulin. Under subsequent urethane anesthesia, pressor and sympathetic responses to hypothalamic stimulation, as well as pressor responses to tyramine and vasopressin, were augmented in insulin-treated rats. A generalized increase in cardiovascular reactivity caused by insulin seemed unlikely since pressor responses to norepinephrine were unaltered. Enhanced hypothalamic responsiveness was considered due to improvement of diabetic encephalopathy rather than to direct CNS stimulation by insulin because the injected insulin had mostly dissipated by the time pressor responses were recorded. By showing that insulin treatment produced changes opposite to those occurring during induction of diabetes our results suggest that insulin can alleviate cardiovascular and hypothalamic dysfunction in streptozotocin-induced diabetes.
Baroreflex sensitivity modulates vasodepressor response to nitroprusside.
Authors: Shepherd A M , Lin M S , McNay J L , Musgrave G E , Keeton T K
Published: June 2012

Baroreflex activity is a determinant of the homeostatic response to alteration in blood pressure. We examined the factors that determine the magnitude of the vasodepressor response to sequential incremental intravenous infusions of sodium nitroprusside (NP), 0.05 to 6.4 micrograms/kg/min, in eight male patients with essential hypertension. Each infusion level was of 10 minutes' duration. Change from control values of mean arterial pressure (delta MAP), heart rate (delta HR) and plasma norepinephrine (delta NE) were obtained at the end of each infusion level. Significant correlations were found between delta MAP vs log dose NP, delta HR vs delta MAP and delta NE vs delta MAP for each patient (p less than 0.05). However, the slopes of these relationships varied widely between subjects and were significantly correlated with the control blood pressure of each patient. In addition, the sympathetic responsiveness, as measured by delta NE vs delta MAP, was inversely correlated with the degree of vasodepressor response seen. Thus, the magnitude of the vasodepressor response was determined by two major factors: 1) the predrug blood pressure, possibly reflecting altered vascular geometry with hypertension; 2) the degree of sympathetic response, which probably acts by mediating the degree of reflex alpha-adrenergic-mediated arteriolar vasoconstriction.
Cardiovascular and sympathetic responses to chronic arachidonate in SHR and WKY rats.
Authors: Bayorh M A , Zukowska-Grojec Z , Ezra D , Feuerstein G Z , Kopin I J
Published: June 2012

In rats between the ages of 4 and 12 or 14 weeks, repeated daily subcutaneous administration of arachidonate (AA) at a dose of 50 or 200 mg/kg significantly retarded the development of hypertension in spontaneously hypertensive rats (SHR) but did not alter the normal age-related increase in blood pressures (BP) of normotensive (WKY) rats. Heart rates (HR) and plasma levels of norepinephrine (NE), but not epinephrine, were lower in AA-treated SHR than in saline-treated animals. AA-treated SHR and WKY gained less weight than the saline-treated controls. In pithed AA-treated SHR, stimulation of the sympathetic outflow (50 V, for 1 minute at 0.3 or 3.0 Hz) and intravenous administration of NE (0.3 or 3.0 g/kg) evoked smaller pressor responses than in saline-treated controls, but the stimulation-evoked increases in plasma catecholamines were unchanged by AA treatment. These results indicated that, in SHR, chronic AA treatment reduces BP by mechanisms that do not directly affect NE release from sympathetic nerves. There appears to be both reduced central nervous system activation of the sympathetic outflow and diminished responses to peripheral sympathetic stimulation and exogeneous NE which may be secondary to the reduced vascular hypertrophy that usually accompanies the development of high BP in SHR.
Dissociation of genetic hyperactivity and hypertension in SHR.
Authors: Hendley E D , Atwater D G , Myers M M , Whitehorn D
Published: June 2012

The Wistar Kyoto strain of spontaneously hypertensive rat (SHR) has been characterized as behaviorally hyperactive as well as hypertensive. The relationship between these two inbred traits remains uncertain, and their coexistence in the SHR has complicated studies of central nervous system mechanisms underlying the hypertensive process. A breeding program was initiated to examine the possible genetic linkage of these two traits which, if separable, would allow us to develop substrains of SHR that are hypertensive without being hyperactive, or hyperactive without being hypertensive. We crossed SHR males with Wistar Kyoto, normotensive (WKY) female rats and produced F1 hybrids which were then randomly inbred to produce an F2 population. When tested at 12 weeks of age, F2 rats exhibited the expected wide range of mean systolic blood pressures (BP), from 111 to 174 mm Hg, as determined using indirect tail plethysmography. The BP in the parental rats at the time of breeding (16 weeks) was 187 +/- 4.5 mm Hg (SHR males, n = 7) and 111 +/- 2.4 (WKY females, n = 7). Locomotor activity was determined in an automated activity cage in F1 and F2 rats at 12 weeks of age. These strains exhibited a wide range of phenotypic distribution of locomotor activity scores, and the mean scores were intermediary between those of SHR rats and WKY rats of the same age. Among individual rats of both the F1 and F2 hybrid strains, there was no correlation between the activity score and the level of the BP at 12 weeks of age. These findings indicated that the genes responsible for the hypertensive trait and those responsible for the hyperactivity trait were not tightly linked in the hybrid populations, suggesting that different genetic factors were involved in the transmission of each of these traits. Accordingly, it should be possible to separate the two traits by further selective, recombinant inbreeding procedures.
Asymptomatic normotensive primary aldosteronism. Case report.
Authors: Matsunaga M , Hara A , Song T S , Hashimoto M , Tamori S , Ogawa K , Morimoto K , Pak C H , Kawai C , Yoshida O
Published: June 2012

We report a case of primary aldosteronism in a 30-year-old woman without hypertension or any other characteristic symptoms. The condition was first suspected by hypokalemia (2.6 mEq/liter), which was incidentally found by routine checkup. There was evidence of suppressed plasma renin activity (PRA) and elevated plasma aldosterone levels. However, the blood pressure never reached a hypertensive level, and the circulating blood volume was within a normal range. A functioning right adrenal tumor was diagnosed by adrenal scintigraphy, computerized x-ray tomography, and adrenal venography. Adrenal venous catheterization suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected, yet the blood pressure remained much the same. Hypertension is not necessarily a sign of primary aldosteronism.
Central resetting of baroreflex in the spontaneously hypertensive rat.
Authors: Gonzalez E R , Krieger A J , Sapru H N
Published: June 2012

The role of central nervous system in the resetting of baroreflex was investigated in 5-month-old spontaneously hypertensive rats (SHR) of Okamoto strain. Age-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. The aortic nerves, which in the rat, contain few or no chemoreceptor fibers, were stimulated electrically using a wide range of stimulus frequencies. The depressor responses (expressed as percent decrease in blood pressure as compared to its blood pressure value prior to aortic nerve stimulation) produced by these stimulations were significantly smaller in SHR than those in WKY. In another series of experiments, changes in the efferent limb of the baroreflex arc (i.e., greater splanchnic nerve activity) in response to stimulation of the baroreceptor afferents in the aortic nerve were recorded. Inhibition of the greater splanchnic nerve activity due to aortic nerve stimulation was found to be significantly smaller in SHR than in the WKY. Control sympathetic nerve activity was greater in SHR than in WKY. These results suggest that the central bulbospinal nervous system may be another site for resetting of baroreflex in hypertension.
Measurements of plasma norepinephrine concentrations in human primary hypertension. A word of caution on their applicability for assessing neurogenic contributions.
Authors: Folkow B , Di Bona G F , Hjemdahl P , Torén P H , Wallin B G
Published: June 2012

The relationship between plasma levels of norepinephrine (NE) and sympathetic neural activity is discussed with special reference to human primary hypertension. Since sympathetic discharge is differentiated, neural activity to a given target organ will contribute variably to plasma NE levels in different situations. Hemodynamically, early primary hypertension is often characterized by a mild defense reaction-like pattern with signs of increased sympathetic activity to the heart and vasoconstriction in the renal and splanchnic vascular beds. Although important hemodynamically, these organs seem to be of less importance as contributors to peripheral plasma NE levels. In contrast, muscle sympathetic activity and muscle vascular resistance is unchanged or reduced. Since this organ mass contributes importantly to plasma NE levels, especially in peripheral venous blood, it is not surprising that most patients with primary hypertension have normal NE levels. It is concluded that NE concentrations in forearm or mixed venous blood are unreliable indicators of sympathetic neural contributions to essential hypertension, tending to underestimate this element, and that regional measurements of NE overflow are needed for a reliable analysis.
Longitudinal study of the hindquarter vasculature during development in spontaneously hypertensive and Dahl salt-sensitive rats.
Authors: Mueller S M
Published: June 2012

The purpose of this study was to examine vascular structural alterations longitudinally in spontaneous and Dahl genetic hypertension. Hypertensive and control animals were studied at 5,9-11, and 17-19 weeks of age to permit analysis of prehypertensive, early and established hypertensive stages. Minimal and maximal resistance of the hindquarter vasculature was used as a functional assessment of structural alterations. At 5 weeks of age, the minimal vascular resistance of the spontaneously hypertensive rats (SHR) was elevated over Wistar-Kyoto (WKY) (p less than 0.02) but there was no difference between Dahl salt-sensitive (S) and resistant (R) rats. In both sets of animals, the minimal vascular resistance of the hypertensive group was significantly elevated over controls with age: p less than 0.001 in SHR; p less than 0.001 in Dahl S. The maximal vasoconstrictor response was significantly greater with age in SHR than in WKY, (p less than 0.001), but was not different in Dahl S compared to R. Thus, structural alterations, determined by assessing minimal vascular resistance, are present in both spontaneous and Dahl salt-sensitive hypertension, but the origin of the two differ. An increase in smooth muscle mass, assessed by maximal constriction, contributes importantly to the structural alterations in spontaneous hypertension; in Dahl S, other factors appear to contribute to structural alterations. Further, structural alterations precede frank hypertension in SHR but not in Dahl S hypertension.
Kidney function and sodium handling in the pregnant spontaneously hypertensive rat.
Authors: Lindheimer M D , Katz A I , Koeppen B M , Ordóñez N G , Oparil S
Published: June 2012

Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.
Endogenous opioids and baroreflex control in humans.
Authors: Rubin P C , McLean K , Reid J L
Published: June 2012

We describe two studies designed to elucidate the role of endogenous opioids in blood pressure control in humans. In the first study, nine normal subjects received infusions of DAMME (a metenkephalin analog), naloxone, or saline, and blood pressure, heart rate, and plasma norepinephrine concentration were determined supine and following 5 minutes of 70 degrees head-up tilt at intervals for 6 hours. Blood pressure following tilt was significantly decreased by DAMME but not influenced by naloxone, the effect being most marked at 3 hours (placebo = 110 +/- 6/78 +/- 7 mm Hg; naloxone = 106 +/- 10/79 +/- 5 mm Hg; DAMME = 96 +/- 16/67 +/- 8 mm Hg (p less than 0.01). However, heart rate and plasma norepinephrine did not rise in response to this hypotension. Heart rates at 3 hours were: placebo = 87 +/- 16 bpm; naloxone = 88 +/- 19 bpm; DAMME = 89 +/- 23 bpm. Plasma norepinephrine levels (nmol/liter) at 3 hours were: placebo = 6.0 +/- 2.2; naloxone = 5.8 +/- 1.9; DAMME = 6.0 +/- 1.9. In the second study, seven normal subjects had blood pressure reduced by incremental infusions of sodium nitroprusside, and the effects of placebo, naloxone, and DAMME on the slope of the heart period/blood pressure relationship investigated. Naloxone significantly increased the slope by 90% and DAMME significantly reduced the slope by 30%. It is concluded that endogenous opioids modulate the baroreflex control of blood pressure in normal humans.
Effects of withdrawing diuretic therapy on blood pressure in mild hypertension.
Authors: Maland L J , Lutz L J , Castle C H
Published: June 2012

A 1-year double-blind placebo-controlled study on the effects of diuretic withdrawal was conducted on a group of 62 previously well-controlled, mildly hypertensive patients. Data were collected on blood pressure (BP), biochemical laboratory values, and subjective reports of side-effects. Twenty-six percent of placebo subjects and 3% of the active treatment subjects reached preset criteria for the return of hypertension (reverters). The average systolic and diastolic pressures of all placebo-treated patients who did not revert showed statistically significant increases. BP control was quickly reestablished in reverters by restarting diuretic therapy. No substantial differences in side-effects were reported between the groups, and laboratory changes were those consistent with known metabolic effects of thiazide and thiazide-like diuretics. This study showed a much lower reversion rate after treatment withdrawal than previously reported by other investigators. It also showed significant increases in BP of placebo patients who did not revert. Long-term diuretic therapy retains its effectiveness in responsive mild hypertensive patients, potentially offering protection against the increased risks of mortality and morbidity associated with even slight elevations of BP. Withdrawal of diuretics cannot be recommended for patients with mild hypertension without use of other equally effective interventions to maintain optimum BP control.
Antihypertensive effectiveness of intravenous labetalol in accelerated hypertension.
Authors: Smith W B , Clifton G G , O'Neill W M , Wallin J D
Published: June 2012

Labetalol, an antihypertensive agent that blocks both beta- and alpha-adrenergic receptors, was administered intravenously to 19 patients with accelerated hypertension who required rapid lowering of blood pressure. Systolic blood pressure was lowered from 209 +/- 4 to 143 +/- 2 mm Hg; diastolic blood pressure was reduced from 140 +/- 2 to 93 +/- 2 mm Hg. Side-effects were minimal and included nausea, epigastric burning, rhinorrhea, and premature ventricular contractions. One patient became hypotensive and required treatment. Overall, the study demonstrates labetalol to be a safe and effective agent for the emergency lowering of blood pressure, with demonstrated results comparable to other parenteral agents.
Reversible renal failure due to captopril in a patient with transplant artery stenosis. Case report.
Authors: Mason J C , Hilton P J
Published: June 2012

A patient who was subsequently shown to have stenosis of the artery to a transplanted kidney sustained three episodes of impaired renal function during treatment with low doses of captopril. On each occasion this was reversed by withdrawal of therapy. The effect was not related to reduction of blood pressure since lower pressures were recorded during treatment with minoxidil, without deterioration of renal function. A possible mechanism involving blockade of the intrarenal renin-angiotensin system is discussed.
Involvement of the baroreceptor reflexes in the changes in blood pressure with sleep and mental arousal.
Authors: Conway J , Boon N , Jones J V , Sleight P
Published: June 2012

We have measured baroreflex sensitivity and blood pressure in 13 subjects during sleep and three stages of progressive mental arousal after waking. Baroreflex sensitivity was measured by correlating the increase in pulse interval with the increase in systolic pressure produced by an intravenous injection of 80 micrograms of phenylephrine. Blood pressure was measured directly from the brachial artery. During sleep, blood pressure fell and baroreflex sensitivity increased; with increasing mental arousal, blood pressure rose and baroreflex sensitivity decreased. These results suggest that baroreflex activity may be involved in the medium-term regulation of blood pressure during the day and night in addition to its recognized role in buffering acute changes in blood pressure.
Plasma norepinephrine and dietary sodium intake in normal subjects and patients with essential hypertension.
Authors: Masuo K , Ogihara T , Kumahara Y , Yamatodani A , Wada H
Published: June 2012

To evaluate the relationship between sodium intake and the activity of the sympathetic nervous system in patients with essential hypertension, plasma catecholamine levels were measured in 49 essential hypertensive patients and 38 age-matched normal subjects under regular-, high-, and low-sodium diets (mean 24-hour sodium excretions; 116 +/- 8, 267 +/- 29, 31 +/- 7 mEq/day, respectively). The levels of plasma norepinephrine were significantly (p less than 0.01) higher in hypertensive patients than in normal subjects. However, they were significantly reduced by high-sodium intake and increased by low-sodium intake in both patients and controls. The percent decrease and change in the absolute plasma norepinephrine levels from low- to high-sodium states were greater in normal subjects than in the hypertensive patients. The results are interpreted as indicating that an abnormal relationship exists between sodium intake and the activity of sympathetic nervous system in patients with essential hypertension.
Cardiovascular hormonal effects of circulating norepinephrine.
Authors: Izzo J
Published: June 2012

The hormonal effects of circulating norepinephrine (NE) were evaluated with two-step NE infusion studies in normal volunteers. At an infusion rate that increased plasma NE 2.5-fold (approximately equivalent to the change from supine to upright posture), there were small but consistent increases in diastolic pressure (+5 mm Hg) and plasma renin activity (+13%). At the high extreme of the physiologic range (a 9-fold increase over supine basal), circulating NE caused major changes in blood pressure (+22/15 mm Hg), heart rate (-7 bpm), and plasma renin activity (+67%). Thus, at physiologic concentrations, circulating NE should be considered to be a cardiovascular hormone as well as an index of sympathetic nervous activity.
Chemical renal medullectomy. Effect on urinary prostaglandin E2 and plasma renin in response to variations in sodium intake and in relation to blood pressure.
Authors: Bing R F , Russell G I , Thurston H , Swales J D , Godfrey N , Lazarus Y , Jackson J
Published: June 2012

We have studied the possible vasodepressor role of the renal medulla by chemical medullectomy. Bromoethylamine hydrobromide (200 mg/kg) was injected to induce selective renal medullary necrosis in rats. The acute effects on sodium balance and long-term effects on blood pressure, plasma renin concentration (PRC) and urinary prostaglandin E2 (PGE2) were studied and compared with saline injected controls. There was an immediate and sustained increase in urine volume of low osmolality. Direct blood pressure in conscious free-moving animals was higher at 2 and 10 weeks after injection in medullary-damaged rats, although this was only significant at 10 weeks (136 +/- 3.3 vs 118 +/- 4.5 mm Hg, p less than 0.01). An initial negative sodium balance returned to normal by 7 days and rats with established medullary damage tolerated a wide range of sodium intakes. Although there was no evidence of sodium retention on the normal diet, with very high sodium loads some sodium retention was apparent since PRC was suppressed and body weight increased. Plasma creatinine and creatinine clearance were normal. PRC in rats with medullary damage was unchanged on normal diet and rose to similar levels as in control rats on low sodium intake. Urinary PGE2 was markedly reduced (148 +/- 54 vs 536 +/- 71 ng/day, p less than 0.01) in medullary damaged rats, consistent with the renal medulla being the major source of urinary PGE2. High salt intake increased urinary PGE2 in normal and proportionally in medullary damaged rats, whereas on a low sodium intake, urinary PGE2 was not different from that on the normal diet in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.
Authors: Hamilton C A , Reid J L
Published: June 2012

Increased pressor responses to norepinephrine and other pressor agents have been reported to occur in human essential hypertension and in several animal models of experimental hypertension. These increased responses might be related to the development of hypertension or could be a secondary consequence of the elevation in blood pressure. We have examined pressor responses to alpha-adrenoceptor agonists and to angiotensin II in male New Zealand White rabbits with perinephritic hypertension. Increased pressor responses were observed for the alpha 1 adrenoceptor agonist phenylephrine and the mixed alpha 1/alpha 2-adrenoceptor agonist norepinephrine but not for the alpha 2 adrenoceptor selective agonist guanabenz or angiotensin II. The increase occurred within 7 days of surgery and in some animals was observed when mean arterial pressure was not significantly elevated. It could not readily be attributed to intimal thickening or hypertrophy of the arterial wall, altered basal levels of norepinephrine or epinephrine, changes in norepinephrine clearance, beta-adrenoceptor interactions, or decreased baroreceptor sensitivity. However, the possibility that vascular hypertrophy and decreased baroreflex sensitivity may contribute to the increase at later times cannot be excluded. In all tissues examined, specific prazosin binding was decreased in the older animals and specific clonidine binding was decreased in forebrain. However, these changes were observed in both hypertensive and sham-operated animals and were probably age-related. We believe the increased response to alpha 1-adrenoceptor agonists may be related to changes at a postreceptor site in the coupling of receptor activation to smooth muscle contraction.
Racial differences in erythrocyte cation transport.
Authors: Weder A B , Torretti B A , Julius S
Published: June 2012

Erythrocyte contents and ouabain-insensitive transport pathways were measured in 120 white and black normotensives and hypertensives. Mean maximal sodium-stimulated lithium-sodium countertransport rate was higher in white hypertensives than in white normotensives, and countertransport was significantly positively correlated with mean arterial pressure in whites. Values similar to those in white normotensives were found in both black normotensives and hypertensives, and countertransport was not significantly correlated with blood pressure in blacks. The rate constant for passive lithium efflux was greater in whites as compared to blacks, and the difference was not related to blood pressure level or sex. Ouabain-insensitive, furosemide-sensitive sodium and potassium effluxes were not found to be altered in hypertension. Furosemide-sensitive sodium efflux rate was lower in blacks but furosemide-sensitive potassium efflux was not similarly depressed. While white subjects demonstrated a close correlation between sodium and potassium effluxes, blacks did not. Further study of these differences in the cellular metabolism of sodium and potassium may provide clues to the pathogenesis of racial dissimilarities in total body sodium handling.
Acute local effects of angiotensin II on the intestinal vasculature.
Authors: Nyhof R A , Rascoe T G , Granger H J
Published: June 2012

The vasotoxic properties of angiotensin II (AII) on vascular endothelial cells have been implicated in the increased extravasation of proteins and water observed in certain forms of chronic arterial hypertension. Since microvascular permeability in the small intestine is increased in one-kidney, one clip hypertension, we tested the hypothesis that AII decreases the permselectivity of intestinal microvessels to plasma proteins. The acute intestinal vascular effects of AII were studied by locally infusing AII into isolated canine jejunal segments. A measure of vascular permeability in control and infused segments was obtained by estimating the osmotic reflection coefficient as 1-lymph/plasma protein concentration ratio when the ratio reached a plateau at high lymph flows. Lymph flows were increased by raising the venous pressure from a control of 5 to 30-35 mm Hg in 5 mm Hg steps. Resting control blood and lymph flows were reduced by AII, but these flows were not different at the higher venous pressures due to the apparent blunting of the venous-arteriolar response by AII. The estimated osmotic reflection coefficient of 0.85 for the control animals was less than that obtained in the infused segments (0.93). This effect was substantiated by electrophoretic separation of protein fractions. Thus, AII per se does not cause an acute increase in intestinal vascular permeability, and may, in fact reduce it.
Cadmium effect on the Na,K-ATPase system in cultured vascular smooth muscle cells.
Authors: Tokushige A , Higashino H , Searle B M , Tamura H , Kino M , Bogden J D , Aviv A
Published: June 2012

The present study focuses on the interaction between cadmium (Cd) and the Na, K-ATPase system in in vitro grown vascular smooth muscle cells (VSMCs) derived from the rat carotid artery. In disrupted VSMCs rendered permeable by osmotic shock, Cd inhibited Na, K-ATPase; I50 was reached at 10(-5) M Cd. Mg-ATPase was also inhibited by Cd; I50 was attained at concentrations of 10(-4) M Cd. Cd inhibition of Na,K-ATPase in the VSMCs was noncompetitive with respect to Na, K, and ATP. Rubidium transport experiments performed with intact VSMCs demonstrated that within an incubation period of 150 minutes, a concentration of 10(-4) M Cd in the extracellular fluid exerted no acute effect on the Na-K pump. Within this time interval, intracellular Cd attained a concentration eightfold higher than the extracellular Cd concentration. Thus, it appears that under acute conditions Cd exerts its inhibitory effect on Na, K-ATPase only in disrupted VSMCs. The data further suggest that, in the VSMC, conditions under which Cd inhibits Na, K-ATPase are consistent with inhibition from the cytoplasmic side of the cell membrane.
Possible role of nutritional factors in the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats.
Authors: Yamori Y , Horie R , Tanase H , Fujiwara K , Nara Y , Lovenberg W
Published: June 2012

The incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats appears to depend on the severity of the hypertension and nutritional factors. Comparison of American and Japanese commercial rat diets revealed a much higher incidence of stroke in rats receiving the Japanese diet (88% vs 30% by 9 months of age). Analyses of the diets indicate that perhaps the most important difference in the two diets is the protein content. Based on complete amino acid analyses of the protein in these diets, it appears that the American diet contains about 22% protein as compared to about 15% for the Japanese diet. Minor differences in vitamin and mineral contents are not remarkable. Comparison of the findings in this experimental rat model with epidemiologic studies suggest that nutritional factors may also play a role in the incidence of stroke in humans.
Progressive microvascular alterations with the development of renovascular hypertension.
Authors: Joshua I G , Wiegman D L , Harris P D , Miller F N
Published: June 2012

Norepinephrine-induced changes in diameters of first- (1A), second- (2A), and third-order (3A) arterioles in the exposed cremaster muscles of normotensive and renovascular hypertensive rats were quantitated via television microscopy. By 2 weeks following the surgery to induce hypertension, we found that 3A sensitivity to norepinephrine had increased and the 1As had chronically constricted. By 4 weeks, the constriction had progressed to include both 1A and 2A. Sensitivity was no longer increased in 3As and, in fact, sensitivity had decreased in 1As and 2As. The 1As and 2As could not be dilated with isoproterenol or nitroprusside; thus, the vessels appeared to have undergone a structural alteration. We suggest from these results that the early increased 3A sensitivity contributes to the initial development of hypertension. The larger arterioles then constrict to protect the downstream vessels from increased luminal pressure. As the hypertension develops, the constriction progresses to smaller arterioles in an attempt to maintain normal pressure in the capillaries (site of water exchange). The constricted arterioles contribute to increased total peripheral resistance, and with the constriction, there occurs a general decrease in vessel responsiveness.
Role of cardiac factors in the initial hypotensive action by beta-adrenoreceptor blocking agents.
Authors: Colfer H T , Cottier C , Sanchez R , Julius S
Published: June 2012

The blood pressure decrease after beta-blockade is delayed and there are little data on the hemodynamic events associated with the initial decrease in blood pressure. The present study measured the hemodynamics of the initial hypotensive action of timolol maleate, a nonselective beta-adrenoreceptor blocking agent, in 10 patients with essential hypertension. Frequent measurements were made for the first 30 hours of treatment, and follow-up measurements made at 3 and 6 weeks. Before treatment, mean arterial blood pressure, cardiac output, and arteriovenous oxygen difference were 115.9 +/- 9.1 mm Hg, 4.65 +/- 1.05 liter/min, and 55.0 +/- 9.6 ml/liter, respectively. At 3 hours after the first dose of timolol, blood pressure had fallen 13.5 +/- 8.2 mm Hg (p less than 0.05). This was preceded by an initial decrease in cardiac output, which was not associated with a simultaneous decrease in blood pressure, and by an increase of arteriovenous oxygen difference. The early, statistically significant, decrease in cardiac output was followed by a return to normal output, which coincided with the onset of blood pressure reduction. The magnitude of the initial decrease of cardiac output and of the initial increase in arteriovenous oxygen difference was significantly correlated to the later decrease in blood pressure (7 hours after first dose). These hemodynamic observations are consistent with the notion that early underperfusions of tissue play a role in the initial hypotensive action of beta-blockers. After 6 weeks, the blood pressure remained lower but the cardiac output was again decreased at that point. As with many antihypertensive agents, there was a difference between the early and late hemodynamic pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic and endocrine changes associated with potassium supplementation in sodium-loaded hypertensives.
Authors: Fujita T , Ando K
Published: June 2012

To clarify the mechanism by which potassium (KCl) protects against the blood pressure rising action of sodium (NaCl), we studied the effects of KCl loading in patients with idiopathic hypertension who, after a period of NaCl restriction, partook of a high NaCl diet. Eleven patients who had taken the KCl supplement (96 mEq/day) during the high NaCl period showed lesser mean blood pressure (MAP) rise with changes in NaCl intake from 25 to 250 mEq/day than 12 patients who had not taken the KCl supplement (p less than 0.001). With a high NaCl diet, the KCl-supplemented patients retained less NaCl, gained less weight, and showed a lesser increase in plasma volume and cardiac output than the non-KCl-supplemented ones. Overall, the increase in blood pressure levels during the high Na diet correlated directly either with changes in plasma volume (p less than 0.05) or with changes in cardiac output (p less than 0.01). The results suggest that KCl may prevent a rise in blood pressure with NaCl loads in hypertensive patients by attenuating the increase in cardiac output, mainly as a result of the natriuresis. Furthermore, plasma norepinephrine was measured to estimate the sympathetic activity, since the sympathetic nervous system is known to control urinary NaCl excretion. From the low NaCl diet to Day 3 of the high NaCl diet, plasma norepinephrine was significantly (p less than 0.01) decreased in the KCl-supplemented patients, whereas it remained unchanged in the non-KCl-supplemented ones.(ABSTRACT TRUNCATED AT 250 WORDS)
Rapid cyclic fluctuations of blood pressure associated with an adrenal pheochromocytoma.
Authors: Ganguly A , Grim C E , Weinberger M H , Henry D P
Published: June 2012

We present a patient with an adrenal pheochromocytoma with an unusual pattern of periodic alternating hypertension and hypotension. Alpha-adrenergic blockade alone failed to affect this pattern, which was abolished only after fluid repletion. The efficacy of volume expansion in ultimately correcting the wide fluctuations of blood pressure implicates a possible reflex neurogenic mechanism for the cyclic changes in blood pressure attributable to intravascular volume contraction.