bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenergic activity and peripheral hemodynamics in relation to sodium sensitivity in patients with essential hypertension.
Authors: Koolen M I , van Brummelen P
Published: June 2012

In 25 outpatients with essential hypertension, sodium sensitivity, defined as the difference in mean arterial pressure (delta MAP) between 2 weeks of high-sodium (300 mmol per day) and 2 weeks of low-sodium (LS) intake (50-100 mmol per day), was studied in relation to the plasma norepinephrine (NE) level, NE release, and pressor response to intravenous NE. In addition, forearm blood flow (FBF) was measured by plethysmography. There were two control periods of regular sodium intake, one of 4 weeks' duration at the beginning of the study and one of 2 weeks' duration at the end. The delta MAP ranged from +18 to -8 mm Hg. The eight patients in whom delta MAP was greater than 10 mm Hg were regarded as salt-sensitive. When compared with salt-insensitive subjects, salt-sensitive patients had higher plasma NE levels in the control period (p less than 0.05) and after 2 weeks of HS intake (p less than 0.01). Sodium sensitivity was directly related to the change in plasma NE between the HS and LS periods (p less than 0.001). The NE release decreased in salt-insensitive subjects whereas it increased in salt-sensitive patients between the LS and HS periods. Changes in NE release were directly related to sodium sensitivity (p less than 0.05). The pressor response to NE was not significantly influenced by changes in sodium intake. The FBF fell in salt-sensitive patients and increased in salt-insensitive subjects between the LS and HS periods. Sodium sensitivity was directly related to the change in forearm vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of vasopressin and the sympathetic nervous system in the early phase of high sodium one-kidney renal hypertension.
Authors: Hinojosa C , Haywood J R
Published: June 2012

This study assessed the contributions of the sympathetic nervous system and arginine vasopressin to the onset of one-kidney, one-wrap (1K1W) renal hypertension in rats fed a high sodium diet. Two weeks before renal wrap or sham wrap, rats were given a high sodium diet and water ad libitum. At 3 days postwrap, resting mean arterial pressure (MAP) was significantly greater in renal-wrapped rats. The contributions of the sympathetic nervous system and vasopressin to blood pressure (BP) were assessed by ganglionic blockade and vascular vasopressin receptor antagonism, respectively. Depressor responses to ganglionic blockade were significantly greater in the normotensive rats as compared to the hypertensive rats. Administration of vasopressin antagonist caused a significant fall in pressure only in wrapped rats. In addition, enhanced pressor responses to bolus injections of vasopressin were observed in hypertensive rats. These results indicate that during this phase of the hypertension there is an activation of the vasopressin pressor system without an increase in neurogenic function. Equalization of arterial pressure occurred only when both systems were blocked, regardless of the order of blockade, which indicated that the sympathetic nervous system and vasopressin interact to maintain the hypertension. Comparison of depressor responses to the blocking agents revealed that the interaction is compensatory in nature since the contributions of the sympathetic nervous system and vasopressin to the maintenance of arterial pressure were greater when the other system was blocked.
Vascular responses to serotonin in steroid hypertensive rats.
Authors: Mecca T E , Webb R C
Published: June 2012

This study investigates the mechanism responsible for increased vascular sensitivity to serotonin in deoxycorticosterone acetate (DOCA)-salt hypertension. Femoral arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. Dose-response curves to serotonin were shifted significantly to the left in arteries from DOCA-salt hypertensive rats compared to those from normotensive rats (ED50:DOCA = 7.1 X 10(-8) M; control = 27 X 10(-8) M). The partial agonistic properties of methysergide were increased in femoral arteries from DOCA-salt hypertensive rats. The competitive antagonism of serotonin by methysergide or ketanserin was similar in arteries from control and DOCA-salt hypertensive rats (pA2: methysergide, control = 10.4, DOCA = 10.5; and ketanserin, control = 10.4, DOCA = 10.4). After cellular calcium (Ca) depletion with EGTA, dose-response curves to Ca were obtained in the presence of serotonin (5.7 X 10(-5) M). The Ca sensitivity of vessels from hypertensive rats was not statistically different from that in arteries from normotensive rats. Contractile responses to serotonin in calcium-free solution following loading of a cellular store with Ca were 50% greater in arteries from DOCA hypertensive rats. These results suggest that the enhanced sensitivity to serotonin in DOCA-salt hypertensive rats is not related to a change in receptor affinity nor to an alteration in transmembrane movement of Ca following receptor activation. The increased serotonin sensitivity is related to an altered mobilization of Ca from a cellular store.
Central cardiovascular effects of physostigmine in humans.
Authors: Janowsky D S , Risch S C , Huey L Y
Published: June 2012

Central cholinergic control of pulse rate and blood pressure has seldom been studied in humans. In the current study we contrasted the cardiovascular effects of the centrally acting cholinesterase inhibitor physostigmine, which increases central and peripheral acetylcholine levels, with those of saline placebo and with those of the non-centrally acting cholinesterase inhibitor neostigmine, which only increases peripheral acetylcholine levels. We found that physostigmine, in contrast to neostigmine and saline, caused significant and often profound increases in pulse rate and blood pressure levels in humans. Thus, we conclude that acetylcholine may have a role in central cardiovascular regulation in humans. We also found that administration of physostigmine may cause net increases in pulse of up to 74 beats/minute, systolic blood pressure increases of up to 50 mm Hg, and diastolic increases of up to 45 mm Hg. Such increases could be dangerous in elderly patients with concomitant cerebrovascular or coronary circulation disorders.
Effect of glandular kallikrein on renin release in isolated rat glomeruli.
Authors: Beierwaltes W H , Prada J , Carretero O A
Published: June 2012

Numerous studies have suggested that a functional relationship may exist between the kallikrein-kinin and the renin-angiotensin systems within the kidney. We investigated the effects of glandular kallikrein on renin release by using an in vitro preparation of isolated rat glomeruli with their attendant arterioles. The effect of kallikrein was studied in the presence or absence of 0.1% bovine serum albumin (BSA) in Krebs superfusion fluid. We also studied the effect of inactivating kallikrein by treatment with phenylmethylsulfonyl fluoride or by inhibiting it with aprotinin. In the absence of BSA, kallikrein caused a 12-fold increase in renin release, from 5.1 +/- 1.2 ng angiotensin I (ANG I)/min to 66.0 +/- 2.27 ng ANG I/min (p less than 0.025). In the presence of BSA, renin release increased twofold, from 13.0 +/- 1.8 ng ANG I/min to 24.3 +/- 4.8 ng ANG I/min (p less than 0.025). The basal level of renin measured when the glomeruli were superfused with BSA-Krebs was two to three times greater than when they were superfused with Krebs alone (p less than 0.001). This finding suggests that media protein inhibited renin loss during either the superfusion or storage of renin samples. Neither phenylmethylsulfonyl fluoride-inactivated nor aprotinin-inhibited kallikrein stimulated renin release. We propose that kallikrein can stimulate renin release in isolated glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)
What is the role of ambulatory blood pressure monitoring in the management of hypertensive patients?
Authors: Pickering T G , Harshfield G A , Devereux R B , Laragh J H
Published: June 2012

Noninvasive ambulatory blood pressure (BP) recording is now clinically available for the evaluation of hypertensive patients. It is well known that pressures measured in the office or clinic are unreliable and that repeated measurements are better at predicting outcome than are single measurements. Several studies have compared the correlation between target organ damage and different measures of BP, and in every instance ambulatory BP measurements have given better correlations than clinic readings. In one prospective study the ambulatory BP readings were more predictive of BP-related morbidity than were clinic readings. Data are now being obtained that will establish normal ranges of BP during ambulatory monitoring, against which values from patients being evaluated for hypertension can be compared. It is concluded that ambulatory BP monitoring is of clinical value for the evaluation of patients with mild hypertension.
Postprandial hyperinsulinemia in patients with mild essential hypertension.
Authors: Singer P , Gödicke W , Voigt S , Hajdu I , Weiss M
Published: June 2012

Glucose tolerance tests and diurnal profiles of glucose, insulin, free fatty acids, serum triglycerides, total and high-density lipoprotein cholesterol levels were performed in 8 male patients with mild essential hypertension as well as in 20 normotensive subjects. Although glucose tolerance and postprandial glucose levels appeared equal in both groups, the insulin response after a glucose load and after each meal was significantly increased in hypertensive subjects as compared with the controls (p less than 0.01). The levels of free fatty acids were higher in the postabsorptive phase of patients with hypertension in comparison to normotensive subjects, but decreased markedly when plasma insulin levels rose after meals. In both subject groups serum triglyceride levels showed the typical postprandial increase. Total and high-density lipoprotein cholesterol levels showed neither diurnal variations nor differences between hypertensive subjects and normotensive controls. Postprandial hyperinsulinemia in patients with mild essential hypertension possibly may provoke lipid accumulation in the arterial wall and therefore may be a relevant risk factor for atherosclerosis in these subjects.
Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats.
Authors: Rapp J P , Dene H
Published: June 2012

Several inbred lines of rats were produced from noninbred stock of Dahl salt-sensitive (S) rats, and several inbred lines were also produced from noninbred stock of Dahl salt-resistant (R) rats. There were significant differences (p less than 0.001) in blood pressure response to a high salt diet among the inbred S lines produced, which indicates that the original S stock obtained from Brookhaven Laboratories is not genetically homogeneous. There were no significant differences in blood pressure among the inbred R lines produced. One inbred strain of S and one inbred strain of R with the appropriate blood pressure responses were ultimately brother-sister mated for more than 20 generations. These inbred strains were called S/JR and R/JR respectively. Fulminant hypertension and marked vascular and renal lesions developed in the S/JR after 3 to 4 weeks on a high salt (8% NaCl) diet, and all S/JR were dead within 8 weeks on the high salt diet. In contrast, R/JR survived well on a high salt diet, and hypertension or vascular and renal lesions did not develop. Hypertension and associated vascular and renal lesions developed in S/JR on a low salt diet (0.4% NaCl), but this took 3 to 4 months. These characteristics are similar to those originally reported by Dahl for his noninbred, continuously selected stocks. The R/JR were found to have mild hydronephrosis at 4 months of age, which probably is genetically determined and which may have been fixed inadvertently in the strain during inbreeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Central beta-adrenergic receptors mediate renal nerve activity during stress in conscious spontaneously hypertensive rats.
Authors: Koepke J P , DiBona G F
Published: June 2012

The effects of intracerebroventricular (i.c.v.) administration of beta-adrenergic receptor antagonists (d,l-propranolol or timolol, 30 micrograms in 2 microL of isotonic saline) on the increased renal sympathetic nerve activity and decreased urinary sodium excretion (UNaV) responses to stressful environmental stimulation (air jet to head) in conscious spontaneously hypertensive rats (SHR) were examined. Before i.c.v. d,l-propranolol or timolol, air stress increased renal activity (68% from 10.6 +/- 2.1 and 63% from 8.2 +/- 0.9 integrator resets/min respectively). In contrast, after i.c.v. d,l-propranolol or timolol in the same conscious SHR, air stress had no effect on renal sympathetic nerve activity (+7% from 8.1 +/- 1.7 and +7% from 5.5 +/- 1.0 integrator resets/min respectively). Air stress decreased UNaV in conscious SHR given i.c.v. saline vehicle (25% from 2.8 +/- 0.5 microEq/min/100 g body weight), but had no effect on effective renal plasma flow or glomerular filtration rate. In contrast, after i.c.v. d,l-propranolol or timolol, air stress had no effect on UNaV (0% from 2.8 +/- 0.5 and +9% from 3.3 +/- 0.3 microEq/min/100 g body weight respectively). Mean arterial pressure increased similarly during air stress with i.c.v. saline-vehicle or beta-adrenergic receptor antagonists. Intravenous administration of the same doses of d,l-propranolol or timolol did not prevent the increased renal sympathetic nerve activity or decreased UNaV responses resulting from air stress. These results suggest that central nervous system beta-adrenergic receptors mediate the increased renal sympathetic nerve activity and decreased UNaV responses resulting from stressful environmental stimulation in conscious SHR.
Angiotensin increases inositol trisphosphate and calcium in vascular smooth muscle.
Authors: Alexander R W , Brock T A , Gimbrone M A , Rittenhouse S E
Published: June 2012

Angiotensin II stimulated the breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the generation of inositol trisphosphate (IP3) in cultured rat aortic smooth muscle cells. The decrease in PIP2 and increase in IP3 levels were rapid (measurable at 5 seconds; maximum IP3 levels at 15 seconds). The time course of these changes was comparable to that of angiotensin II-induced increases in cytosolic free calcium, as measured by the calcium-sensitive fluorescent indicator quin 2. The IP3 formation was not stimulated by the calcium ionophore A23187 (5 microM), nor were angiotensin II-induced changes in IP3 formation inhibited by the removal of extracellular calcium with EGTA. Angiotensin II appears to be capable of generating more IP3 than is required for maximal release of intracellular calcium. These data are consistent with the hypothesis that generation of IP3 plays a role in the angiotensin II-induced mobilization of calcium from intracellular storage sites in vascular smooth muscle cells.
Prevention of coronary vasodilator reserve decrement in spontaneously hypertensive rats.
Authors: Tomanek R J , Wangler R D , Bauer C A
Published: June 2012

Spontaneously hypertensive rats (SHR) demonstrate an elevated minimal coronary vascular resistance by the seventh month of age. In an attempt to determine the role of long-standing hypertension in the etiological process of the elevated minimal coronary vascular resistance, we treated SHR and normotensive Wistar-Kyoto rats (WKY) with the vasodilator hydralazine from the time of weaning (1 month) until they were 7 to 8 months of age. The animals were instrumented 24 hours after their last drug dose and then studied on the following day. Using microspheres we measured myocardial perfusion in conscious rats at rest and during maximal coronary dilation induced with dipyridamole infusion. Hydralazine maintained arterial blood pressures in the normotensive range throughout the experimental period, but had little effect on left ventricular weight/body weight ratios (control SHR = 2.95 +/- 0.07, treated SHR = 2.73 +/- 0.08, control WKY = 2.39 +/- 0.09, mean +/- SEM). In treated SHR, left ventricular minimal coronary vascular resistance (per 100 g of tissue) was markedly lower (0.10 +/- 0.01) than in the controls (0.16 +/- 0.01) and not significantly different from that of WKY (0.11 +/- 0.01). Similar differences were noted in the nonhypertrophic right ventricle (treated SHR = 0.08 +/- 0.01, control SHR = 0.16 +/- 0.01, control WKY = 0.10 +/- 0.01). Total minimal coronary vascular resistance was also lower in both ventricles of the treated SHR compared with their nontreated controls. In WKY, hydralazine treatment significantly reduced blood pressure and total minimal coronary vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Is calcium more important than sodium in the pathogenesis of essential hypertension?
Authors: McCarron D A
Published: June 2012

The hypothesis that abnormalities of calcium homeostasis at both an organ and cellular level are a primary factor in the pathogenesis of human and experimental hypertension forms the basis of this review. The rapidly expanding data base relating disordered calcium metabolism to altered vascular smooth muscle function and increased peripheral vascular resistance is summarized and integrated with the observations that reduced dietary calcium intake is the most consistent nutritional correlate of hypertension in the United States. The role of sodium and sodium chloride in pathogenesis of hypertension is reassessed in the light of new data from epidemiological clinical research, experimental models, and cell physiology investigations. The data supporting the thesis that the effects of sodium or chloride or both on blood pressure may represent, in selected situations, secondary influences mediated through induced changes in calcium homeostasis are presented. The interface between these nutritional factors and the normal regulation of vascular smooth muscle is discussed, providing a theoretical framework in which to assess the current information and to formulate the necessary future research.
Rat platelets activate high molecular weight atrial natriuretic peptides in vitro.
Authors: Trippodo N C , Januszewicz A , Pegram B L , Cole F E , Kohashi N , Kardon M B , MacPhee A A , Frohlich E D
Published: June 2012

Evidence suggests that the more biologically active low molecular weight forms (less than 10,000) of rat atrial natriuretic peptides are proteolytically derived from a less active precursor of higher molecular weight. Conversion and activation could occur within the myocyte as well as during circulation. The present study found that in vitro rat blood and platelets were capable of converting the high molecular weight atrial natriuretic peptides (greater than 10,000) to low molecular weight atrial natriuretic peptides within minutes and that enhanced biological activity attended the conversion. Rat high molecular weight peptides were partially purified by gel filtration, lyophilized, and reconstituted in Krebs-Ringer bicarbonate buffer. One milliliter of fresh rat blood was incubated with the high molecular weight peptides at 37 degrees C for 2 minutes. After centrifugation, the supernatant was fractionated on Sephadex G-75. Natriuretic activity was determined by bioassay in anesthetized rats. In contrast to the results following incubation of high molecular weight peptides in Krebs-Ringer bicarbonate buffer alone, which showed that 95% of the natriuretic activity remained in the high molecular weight peptide region, the natriuretic activity of the blood-treated high molecular weight peptides eluted almost exclusively in the low molecular weight peptide region, which indicates conversion. Blood was separated into plasma, erythrocytes, lymphocytes, and platelets. Conversion of high to low molecular weight peptides occurred only after incubation with platelets. Compared with control high molecular weight peptides, rat platelet-treated high molecular weight peptides had significantly greater activity in relaxing histamine-contracted rabbit aortic smooth muscle (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Increased cardiac performance in mild essential hypertension. Left ventricular mechanics.
Authors: Lutas E M , Devereux R B , Reis G , Alderman M H , Pickering T G , Borer J S , Laragh J H
Published: June 2012

To analyze cardiovascular dynamics in essential hypertension, 81 subjects with untreated mild essential hypertension (mean blood pressure, 112 +/- 14 mm Hg) and 87 normotensive subjects from the same working population were studied by echocardiography and simultaneous blood pressure determination. Hypertensive subjects had significantly higher pulse pressure, stroke volume index, cardiac index, left ventricular internal dimension, end-systolic pressure/volume ratio, end-systolic stress, left ventricular mass index, and relative wall thickness than normotensive subjects. Among both normotensive and hypertensive subjects, cardiac performance was closely dependent on afterload, as indicated by close inverse linear relationships between left ventricular fractional shortening and log end-systolic stress (r = -0.83 and -0.78 respectively; both, p less than 0.001). However, 19 of 81 hypertensive patients (23%) fell above the 95% confidence limits of this relationship in normotensive subjects (p less than 0.001 compared with that in normotensive subjects), with a bimodal distribution of fractional shortening as a percent of predicted in relation to end-systolic stress among patients with essential hypertension. This subgroup of hypertensive subjects, with increased resting cardiac performance independent of afterload, was similar in age to the remaining hypertensive subjects but had higher fractional shortening (41 +/- 5% vs 35 +/- 7%; p less than 0.001) and cardiac index (4.3 +/- 1.3 L/min/m2 vs 3.4 +/- 1.0 L/min/m2; p less than 0.005) and lower total peripheral resistance (1257 +/- 502 dyn sec cm-5 vs 1582 +/- 584 dyn sec cm-5 p less than 0.05) and left ventricular relative wall thickness (0.34 +/- 0.06 vs 0.42 +/- 0.10; p less than 0.005). Thus, analysis of cardiac mechanics detected a subset of patients with essential hypertension in whom increased cardiac function cannot be attributed either to relative youth or to supercompensatory left ventricular hypertrophy.
Response of cerebral arteries to sympathetic stimulation during acute hypertension.
Authors: Tamaki K , Heistad D D
Published: June 2012

Our goal was to determine whether sympathetic stimulation during acute hypertension constricts large cerebral arteries and attenuates increases in cerebral microvascular pressure. We measured cerebral blood flow with microspheres and pressure in small pial arteries with a servonull device in anesthetized cats. During moderate hypertension, sympathetic stimulation had little effect on resistance of large or small cerebral vessels. During severe hypertension, sympathetic stimulation prevented passive decreases in resistance of large cerebral arteries and allowed pronounced constriction of small vessels. During hypertension, there was a large increase in pressure in small pial arteries. Although sympathetic stimulation prevented decreases in resistance of large arteries during severe hypertension, it did not attenuate increases in pressure in pial arteries approximately 200 micron in diameter and only modestly attenuated increases in pressure in pial arteries approximately 100 micron in diameter. These findings indicate that sympathetic stimulation has important effects on resistance of both large and small cerebral vessels during severe hypertension. Thus, although stimulation produces dilation of small cerebral vessels during normotension, sympathetic stimulation allowed constriction of small vessels during severe hypertension. These results also indicate that sympathetic stimulation does not prevent increases in pressure in small pial arteries. Thus, protection of the blood-brain barrier by stimulation of sympathetic nerves during hypertension is not the result of attenuation of increases in pial artery pressure.
Race and cardiovascular reactivity. A neglected relationship.
Authors: Murphy J K , Alpert B S , Moes D M , Somes G W
Published: June 2012

The magnitude of the cardiovascular response to stress has been implicated in the pathogenesis of cardiovascular disease. Psychological stress procedures have received increased usage as an alternative to expensive physical (exercise) stress procedures. In the present investigation, 213 healthy, black or white, male or female children between the ages of 6 and 18 years were exposed to the psychological stress of a video game. The video game challenge was administered by a black or a white experimenter and was played under three levels of increasing stress, 1) personal challenge, 2) experimenter's challenge, and 3) experimenter's challenge accompanied by a financial incentive, while blood pressure and heart rate were monitored. Results indicated that the video games provoked significant and incremental cardiovascular reactivity across the games. Black children demonstrated significantly greater reactivity than white children; the racial difference was more reliably observed for systolic and diastolic blood pressure than for heart rate. Furthermore, the race of the experimenter exerted a significant effect and often interacted with the race of the child, such that greater reactivity occurred in same-race pairings than in mixed-race pairings. These results suggest that reactivity is affected by an individual's race and social milieu and that reactivity may be one mechanism responsible for the greater prevalence of hypertension among blacks.
Mechanisms by which nephrectomy stimulates adrenal renin.
Authors: Baba K , Doi Y , Franco-Saenz R , Mulrow P J
Published: June 2012

Renin has been identified in the adrenal gland by several investigators. Nephrectomy is the most potent stimulator of adrenal renin, and in the present study we investigated the mechanism by which nephrectomy stimulates adrenal renin. The pituitary plays a permissive role since hypophysectomy abolished the response of adrenal renin to nephrectomy (from 117.3 +/- 14.55 to 10.37 +/- 1.63 ng angiotensin I/mg protein/hr) and adrenocorticotropic hormone (ACTH) treatment restored the response to nephrectomy in hypophysectomized rats to 120 +/- 20.62 ng angiotensin I/mg protein/hr. However, large doses of ACTH given to intact rats did not increase adrenal renin to the high level observed after nephrectomy. Potassium also plays an important role, since prevention of hyperkalemia after nephrectomy by treatment with a cation exchange resin, sodium polystyrene sulfonate (Kayexalate), significantly reduced the adrenal renin response to nephrectomy. A third factor involved is the lack of negative feedback by plasma angiotensin II. Infusion of angiotensin II intraperitoneally prevented the rise in adrenal renin after nephrectomy (from 65.25 +/- 7.60 to 9.27 +/- 0.99 ng angiotensin I/mg protein/hr) despite an increase in plasma potassium and corticosterone. In conclusion, three factors influence the response of adrenal renin to nephrectomy: 1) the pituitary through the release of ACTH, 2) a direct stimulation by high plasma potassium levels, 3) the lack of angiotensin II feedback inhibition. Whether the high adrenal renin contributes to the high aldosterone observed in rats after nephrectomy remains to be established.
Renal and systemic effects of enalapril in chronic one-kidney hypertension.
Authors: Woods R L , Anderson W P , Korner P I
Published: June 2012

We have investigated the role of angiotensin II in the development of high blood pressure and in the maintenance of renal function during 2 weeks of one-kidney renal artery stenosis in conscious dogs. Responses to a fixed degree of inflation of a balloon cuff around the renal artery were compared in dogs with or without continuous enalapril (MK 421) treatment. In six untreated dogs, mean aortic pressure was increased by 17.1 +/- 2.0 mm Hg, due primarily to increases in total peripheral resistance with little change in cardiac output, while glomerular filtration rate, renal blood flow, renal artery pressure, and plasma renin activity were back to prestenosis levels. In seven enalapril-treated dogs mean aortic pressure was increased by 23.0 +/- 2.7 mm Hg and was not significantly different from that occurring in untreated dogs. This rise was due to increases in total peripheral resistance (10%) and cardiac output (12%). In the absence of angiotensin II, glomerular filtration rate remained low, at only 56 +/- 6% of prestenosis levels. Renal blood flow returned to normal, but the renal artery pressure remained 25% lower than control values. Thus, the main role of angiotensin II in chronic one-kidney Goldblatt hypertension does not appear to be through its pressor properties but rather through its actions in the kidney to preserve glomerular filtration. This effect on renal function persisted throughout the course of the hypertension, even when the plasma renin levels returned to normal.
Arterial baroreflexes and blood pressure and heart rate variabilities in humans.
Authors: Mancia G , Parati G , Pomidossi G , Casadei R , Di Rienzo M , Zanchetti A
Published: June 2012

The factors responsible for 24-hour blood pressure and heart rate variabilities have never been clarified; however, studies performed in unanesthetized animals have shown an increase in blood pressure variability after sinoaortic denervation, and a negative relationship has been reported occasionally between blood pressure variability and baroreflex control of heart rate in humans. We have systematically investigated this issue in 82 ambulant hypertensive subjects using 24-hour intraarterial blood pressure recording (Oxford method) in which blood pressure and heart rate variabilities were measured by calculating the standard deviations of the values obtained throughout the 24 hours or during separate daytime and nighttime periods. Baroreflex sensitivity was assessed by the bradycardic or tachycardic responses to intravenous injections of phenylephrine or nitroglycerin and by the blood pressure response to changes in carotid transmural pressure obtained with a neck chamber. The sensitivity of the baroreceptor-heart rate reflex as assessed by the vasoactive drug technique showed a negative relationship with 24-hour blood pressure variability as well as with daytime and nighttime blood pressure variabilities measured separately (r = -0.28 to -0.50, p less than 0.05). These variabilities also correlated negatively with the sensitivity of the baroreceptor-blood pressure reflex as assessed by the neck chamber technique. By contrast, baroreflex sensitivity showed a positive correlation with heart rate variabilities (r = 0.32 to 0.47, p less than 0.05). The relationship between baroreflex sensitivity and blood pressure and heart rate variabilities was confirmed when the data were analyzed by multiple regression to adjust for blood pressure and age differences among the 82 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic effect of ketanserin in mild to moderate essential hypertension.
Authors: Woittiez A J , Wenting G J , van den Meiracker A H , Ritsema van Eck H J , Man in't Veld A J , Zantvoort F A , Schalekamp M A
Published: June 2012

Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.
Power dissipation as a measure of peripheral resistance in vascular networks.
Authors: Borders J L , Granger H J
Published: June 2012

Peripheral resistance was examined in the microcirculation of the rat cremaster muscle using a network-conserved parameter, power dissipation. Previous studies of peripheral resistance used network-sensitive parameters, and their interpretation is limited by tacit assumptions about the structure of the peripheral vasculature. Power dissipation is directly linked to the resistive process, providing a measure of resistance based on the actual hemodynamics of the network. The dissipation parameter was quantified with the usual vascular parameters of velocity and vessel segment length; 991 segment lengths were measured in 12 normotensive Wistar-Kyoto rats and 16 spontaneously hypertensive rats. Arterial power dissipation was significantly elevated over a wide range of vessel segments; blood flow ranged from 0.08 to 80 nl/sec. Since the largest vessels showed the greatest power dissipation, the organ resistance elevation seen in hypertension in the cremaster apparently is mediated by the larger vessels in the high flow range. Vessel segment length and number of dissipative vessels were unchanged. The increase in power dissipation was due to a network-averaged reduction in mean vessel diameter. Power dissipation also increased significantly in the fastest flowing venous microvessels (greater than 25 nl/sec), also due to a reduction in vessel segment diameter.
Selective vasodilation produced by renal denervation in adult spontaneously hypertensive rats.
Authors: Krueger A D , Lee J Y , Yang P C , Papaioannou S E , Walsh G M
Published: June 2012

The kidneys of adult male spontaneously hypertensive rats (SHR) were denervated, and systemic and regional blood flows were measured 3 to 5 hours or 5 days after denervation. Arterial pressure was reduced 20 to 27% in denervated SHR during both periods compared with that in sham-operated SHR (iliolumbar blood vessels painted with phenol). This hypotensive response was produced by a 32 to 35% reduction in total peripheral resistance. At 3 to 5 hours and at 5 days, a major decrease in total peripheral resistance was produced by vasodilation in the kidneys and splanchnic organs. Acute urine output, sodium excretion, and plasma renin activity in response to a saline load were not different between sham-operated and denervated SHR. The decreased total peripheral resistance in denervated SHR may have been secondary to a decreased central sympathetic nerve activity revealed by a decreased maximum response to ganglionic blockade. The results suggest that a pathophysiological link may exist between the kidneys and splanchnic organs in genetic hypertension and that specific efferent antiadrenergic or antiafferent nerve therapy, or both, in the kidney may lead to substantial specific decreases not only in renal vascular resistance but also in splanchnic vascular resistance and total peripheral resistance.
Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?
Authors: Connell J M , Kenyon C J , Corrie J E , Fraser R , Watt R , Lever A F
Published: June 2012

Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p less than 0.01). Neither administration of dopamine (1 microgram/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Hyperreactivity of platelets from spontaneously hypertensive rats. Role of external magnesium.
Authors: Baudouin-Legros M , Dard B , Guicheney P
Published: June 2012

Thrombin-induced serotonin secretion from platelets from age-matched spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was compared in the presence of different Ca2+ and Mg2+ concentrations. Platelets from SHR were more reactive than those of WKY, and the difference was more marked in 11-week-old than in younger rats. The responses to three concentrations of extracellular Ca2+ and one extracellular Mg2+ concentration of 10(-3) M were compared. A high external Ca2+ concentration (2 X 10(-3) M) increased secretion in platelets of both strains without suppressing the difference between them. Platelets from SHR were more sensitive than those from WKY to a low external Ca2+ concentration (2 X 10(-6) M). Platelet secretion which is independent of external Ca2+ concentration was higher in platelets from SHR than in those from WKY. External Mg2+ exerted an inhibitory effect on serotonin secretion in both types of platelets, but platelets from SHR were less sensitive to Mg2+ than were those from WKY. This inhibitory effect appeared to be complex. It could be observed in the absence of external Ca2+, and in this case, the difference in reactivity between platelets SHR and WKY depended on the external Mg2+ concentration (up to 2 X 10(-3) M). Furthermore, a Mg2+ -induced antagonism of the stimulatory effect of external Ca2+ concentration appeared at higher concentrations of extracellular Mg2+ and was more potent in platelets from WKY than in those from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of atrial natriuretic factor on angiotensin II-induced hypertension in rats.
Authors: Yasujima M , Abe K , Kohzuki M , Tanno M , Kasai Y , Sato M , Omata K , Kudo K , Takeuchi K , Hiwatari M
Published: June 2012

To assess the physiological role of atrial natriuretic factors in blood pressure regulation, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino acid residues (Arg 102-Tyr 126) in rats with angiotensin II-induced hypertension. Rats were studied while on a normal sodium diet or during sodium loading with 1% NaCl solution used as drinking water. Systolic blood pressure decreased slightly during combined infusion of synthetic atrial natriuretic factor, 150 micrograms/kg/day, and angiotensin II, 900 micrograms/kg/day. This effect was sustained for 3 days in rats receiving a regular sodium intake (p less than 0.01) and during sodium loading (p less than 0.01). Administration of synthetic atrial natriuretic factor to rats made hypertensive by a 3-day infusion of angiotensin II reduced blood pressure slightly, but not to control levels, and this effect was sustained for the remaining 3 days of the experiment in both dietary groups. These results indicate that a nonhypotensive dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of angiotensin II. Thus, the attenuating effect may be involved in blood pressure regulation independently of sodium metabolism, although its actual physiological importance remains undetermined.
The gene for the atrial natriuretic factor is expressed in the aortic arch.
Authors: Gardner D G , Deschepper C F , Baxter J D
Published: June 2012

The gene for atrial natriuretic factor is expressed within the adventitial cells of the rat aortic arch. Atrial natriuretic factor transcripts, similar in overall size (1100-1200 nucleotides) and 5'-termini to those found in the atria, were identified in the arch. Much lower levels (approximately 10-20%) of these transcripts were present in distal thoracic aorta. Atrial natriuretic factor peptide was localized by immunocytochemistry to the adventitia of the arch in regions thought to harbor the aortic baroreceptors. These data suggest a previously unsuspected role for the peptide in regulating systemic blood pressure through the baroreceptor reflex.
Alcohol consumption and hypertension.
Authors: MacMahon S
Published: June 2012

An increased prevalence of hypertension in groups with high alcohol consumption has been recognized for a number of years. More recently, several studies have suggested an independent association between alcohol consumption and blood pressure levels in samples from general populations. Of 30 cross-sectional population studies reviewed, the majority reported small but significant elevations in blood pressure in those consuming three drinks or more per day in comparison with nondrinkers. In 25% of studies, elevations in blood pressure were also reported at lower levels of consumption; in about 40%, the blood pressure of nondrinkers was greater than that of those consuming one to two drinks per day. In two studies, one from the United States and one from Australia, the maximum contribution to the prevalence of hypertension of alcohol consumption greater than two drinks per day was estimated to be 5 to 7%; the contribution in men (11%) was greater than that in women because of their greater alcohol consumption. A prospective association of alcohol consumption with change in blood pressure was observed in five studies. In a small number of experimental studies, short-term falls in blood pressure accompanied alcohol restriction in both normotensive and hypertensive subjects. Uncontrolled observations in heavy drinking populations suggest that the effect on blood pressure of alcohol withdrawal may be lasting. However, firm conclusions about the long-term effects of alcohol restriction, particularly in moderate consumers who represent a large proportion in many populations, must await long-term controlled trials.
Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli.
Authors: Wright C E , Angus J A , Korner P I
Published: June 2012

The local responses of the resistance vessels of the hindquarters of conscious, renal hypertensive (cellophane wrap) and sham-operated normotensive rabbits were studied during infusions of constrictor (norepinephrine, methoxamine, angiotensin II) and dilator (acetylcholine, adenosine, serotonin) drugs. The rabbits had implanted Doppler ultrasonic flow probes on the lower aorta and an indwelling catheter for intra-arterial infusion of drugs. Autonomic blockade with mecamylamine and propranolol was used to determine local vascular effects of each drug uncomplicated by reflex changes. Logistic dose-vascular response curves were characterized by their range from resting to maximum response, their 50% effective dose (i.e., sensitivity or dose at middle of the response range), and the average slope about the 50% effective dose. At maximum dilatation the vascular resistance was about 70% greater in hypertensive rabbits than in normotensive rabbits. There were no significant differences in 50% effective dose values between curves for hypertensive and normotensive rabbits for constrictor or dilator drugs. However, with all drugs the hypertensive rabbits showed about twice the change in vascular resistance per unit dose compared with the normotensive rabbits. These results suggest that hypertrophy of the muscles of the precapillary vessels makes them a nonspecific amplifier of vascular resistance changes evoked by constrictor and dilator stimuli. They do not support previous claims of specific changes in "sensitivity" or claims that local amplifier action is unimportant in hypertension.
Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.
Authors: Lechi A , Lechi C , Bonadonna G , Sinigaglia D , Corradini P , Polignano R , Arosio E , Covi G , de Togni P
Published: June 2012

Intracellular free calcium, [Ca2+]i, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca2+]i was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 +/- 5.0 vs 143.2 +/- 3.1 nmol/L; p less than 0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca2+]i in both the presence and absence of extracellular calcium. This [Ca2+]i increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p less than 0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca2+]i increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca2+]i but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.