bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of gender in centrally induced angiotensin II hypertension in dogs.
Authors: Doursout M F , Chelly J E , Wouters P , Lawrence C , Liang Y Y , Buckley J P
Published: August 2012

This study was designed to investigate the relation between gender, an endogenous inhibitor of the Na+-K+ pump, and volume-dependent hypertension induced by stimulation of the brain renin-angiotensin system and increased salt intake. Angiotensin II (20 ng/min i.c.v.) was infused for 4 weeks in five dogs of each sex with saline as the drinking fluid. In male dogs, angiotensin II induced parallel pressor (30%) and dipsogenic responses (70%), whereas no hypertension and no increase in fluid intake were observed in females. In contrast, the activity of the Na+-K+ pump as assessed by 86Rb uptake was independent of gender. Our data provide novel evidence that gender plays a determining role in the physiological properties of centrally administered angiotensin II.
Pathways of angiotensin formation and function in the brain.
Authors: Ferrario C M , Barnes K L , Block C H , Brosnihan K B , Diz D I , Khosla M C , Santos R A
Published: August 2012

New findings from this laboratory suggest that fragments of angiotensin derived from the amino (N-)terminus are biologically active end products of the renin-angiotensin system. In vitro and in vivo experiments revealed that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] is a major endogenous product of the renin-angiotensin system cascade in the brains of rats and dogs. Additional studies with enzyme inhibitors showed that Ang-(1-7) is produced directly from angiotensin I by an enzyme other than the angiotensin converting enzyme. Immunocytochemical fibers within the hypothalamo-neurohypophyseal vasopressinergic system of the rat. Although Ang-(1-7) is as potent as angiotensin II (Ang II) in stimulating release of vasopressin from superperfused hypothalamo-neurohypophyseal explants, the heptapeptide has no dipsogenic or vasoconstrictor activity. In contrast, Ang-(1-7) mimics the effects of Ang II in augmenting the intrinsic discharge rate of neurons within the vagal-solitary complex and in causing monophasic depressor responses after microinjection into the medial region of the nucleus tractus solitarii. The evidence obtained in these experiments suggests novel mechanisms for the generation of angiotensin peptides in the brain. Additionally, the findings suggest that some of the biological actions ascribed to Ang II might be conveyed by the endogenous production of other angiotensin peptides that are generated by enzymatic pathways alternate to those described in the peripheral circulation.
Sodium intake modulates the development of cardiac hypertrophy in two-kidney, one clip rats.
Authors: Gallo A , Taquini C M , Fontán M , Campissi R , Kuraja I , Gomez Llambí H , Taquini A C
Published: August 2012

Sodium homeostasis exerts a powerful influence on the cardiovascular system in normotensive and hypertensive animals. Previous studies indicate that factors other than blood pressure can influence cardiac hypertrophy. In the present experiments, we evaluated the effects of different sodium diets in the two-kidney, one clip hypertension model in the rat. After the renal artery had been clipped, the rats received a normal sodium (177 meq/kg), high sodium (517 meq/kg), and low sodium (7 meq/kg) diet during 4 weeks. The final blood pressure was almost the same in the three groups (normal sodium 170 +/- 12 mm Hg; low sodium 168 +/- 4 mm Hg; and high sodium 162 +/- 7 mm Hg). Sodium restriction significantly reduced the development of cardiac hypertrophy as compared with rats on normal or high sodium diets. Thus, ventricular weight and ventricular weight/body weight ratio were significantly higher in rats subjected to a normal or high sodium diet (p less than 0.01). The hypertrophied hearts of rats on normal and high sodium diets showed a larger increase in the number of cardiac beta-adrenergic receptors than those observed in hearts from low sodium diet, clipped rats. These results show that sodium modulates the development of cardiac hypertrophy in two-kidney, one clip hypertensive rats. Similarly, the cardiac beta-adrenergic receptors appear to be influenced by dietary sodium intake. A possible role of the sympathetic nervous system is suggested.
Development of renovascular hypertension after central serotonin depletion.
Authors: Trolliet M R , Kurnjek M L , Mikulic L , Basso N , Taquini A C
Published: August 2012

The participation of the central serotonergic system in the development of two-kidney, two clip (2K2C) Goldblatt renovascular hypertension in the rat has been examined. Half of the rats were treated with desmethylimipramine intraperitoneally and 5,7-dihydroxytryptamine intracisternally; the other half received only desmethylimipramine and the 5,7-dihydroxytryptamine vehicle. Two days later, a silver clip was placed in both renal arteries in half of the rats of each group. A sham operation was performed in the remaining rats. Blood pressure was recorded during the 5 weeks after treatment. At the end of the experiment, blood and cerebrospinal fluid samples were obtained. The brain was dissected into several areas and kept frozen. Norepinephrine, serotonin, angiotensinogen, and renin-like concentration were evaluated in the brain areas. Plasma renin activity and angiotensinogen concentration in the plasma and cerebrospinal fluid were estimated. In the sham-operated groups, blood pressure was lower in the treated than in the control rats. The curve of blood pressure increase, as well as the final blood pressure, was similar in the treated and control 2K2C rats. Serotonin was significantly depleted by the 5,7-dihydroxytryptamine treatment in all brain areas. Treatment did not induce any changes in central norepinephrine concentration. Plasma renin activity was diminished in the treated sham-operated rats. These data indicate that the central serotonin depletion does not prevent the development of hypertension and confirm the role of the amine in normal blood pressure regulation. On the other hand, the peripheral renin-angiotensin system might participate in the development of high blood pressure in serotonin-depleted animals.
An evolutionary perspective on salt, hypertension, and human genetic variability.
Authors: Jackson F L
Published: August 2012

Natural selection for electrolyte conservation has likely been the norm throughout human evolutionary history. However, the current patterns of excessive dietary salt intake create the potential for salt overload. Under these conditions, hypertension may be considered an expected pathological response to an evolutionarily new constraint. The transatlantic Middle Passage may have created a genetic bottleneck for salt conservation in African-Americans. Although the initial consequences of this important historical event probably constricted genetic variability and further magnified the potential for salt-sensitive hypertension, the Middle Passage undoubtedly also served as a more generalized major source of environmental stress and may have stimulated subsequent hereditary diversity in the survivors of this holocaust and their descendants. Accelerated rates of mutation, genetic recombination, and transposable genetic elements in conjunction with enhanced opportunities for gene flow, new selective pressures, and drift have all contributed to the tremendous heterogeneity of contemporary African-Americans. It is unlikely that a single genetic event, even of the severity of the Middle Passage, can account comprehensively for the apparent susceptibility of this macroethnic group to high blood pressure and hypertension.
A consensus approach to electrolytes and blood pressure. Could we all be right?
Authors: McCarron D A
Published: August 2012

This commentary sets forth the hypothesis that the putative beneficial or detrimental effects of specific electrolytes on blood pressure regulation in fact reflect highly integrated responses to interactions among these cationic and anionic species. In this paradigm, the impact of any given intake of an electrolyte on arterial pressure will be influenced by the concurrent consumption of other electrolytes. Thus, the heterogeneous blood pressure response in humans to isolated manipulations of nutrients such as sodium, calcium, and potassium may be determined, in part, by the adequacy of the dietary intake of other mineral elements. If this hypothesis is validated by continued research in this area, we would have new strategies available to improve blood pressure control in humans. For example, treatment of "NaCl sensitivity" in some humans might be more effectively approached by correcting dietary deficiencies of either potassium or calcium than by restricting dietary NaCl.
Research and policy directions. Salt and blood pressure.
Authors: Kuller L H
Published: August 2012

The relation between dietary intake of sodium chloride and blood pressure levels remains controversial. The critical questions concern whether there is a susceptible subgroup at risk of elevated blood pressure because of sodium chloride consumption. If there is such a subgroup, what is its size and how can it be identified? Further clinical trials are needed to determine the long-term effects of sodium chloride reduction on blood pressure. The risk of disease, including stroke and coronary heart disease, is linear with blood pressure levels. A small change in blood pressure can have a relatively large impact on disease, even within the normal range of blood pressure.
Sympathetic neural contribution to salt-induced hypertension in Dahl rats.
Authors: Mark A L
Published: August 2012

The Dahl strain provides a model for examining mechanisms involved in the genetic sensitivity or resistance to salt-induced hypertension. Dahl salt-sensitive rats develop hypertension when fed a high salt diet; Dahl salt-resistant rats remain normotensive. Based on early experiments, it was thought that hypertension in Dahl salt-sensitive rats epitomized the overriding importance of renal and humoral mechanisms in salt-induced hypertension, but studies in the past 15 years have demonstrated that alterations in sympathetic neural mechanisms also participate critically in the genetic predisposition to salt-induced hypertension in Dahl salt-sensitive rats. This article briefly reviews sympathetic neural mechanisms in Dahl rats, including evidence for a role of afferent baroreceptor as well as central neural and peripheral adrenergic mechanisms in salt-induced hypertension in Dahl salt-sensitive rats.
Relation between sodium intake, renal function, and the regulation of arterial pressure.
Authors: Osborn J L
Published: August 2012

The long-term regulation of arterial pressure requires the maintenance of a balance between sodium and water intake and sodium and water excretion. Normal salt and water balance leads to stable body fluid volumes and the maintenance of normal renal function is critical to establishing extracellular fluid volume homeostasis. This review focuses on the role of the kidney in the long-term control of salt and water balance with particular emphasis on the relations between sodium intake, the renin-angiotensin-aldosterone system, renal sympathetic nerve activity, and the regulation of arterial pressure via renal sodium and water excretion. The accumulation of evidence in recent years demonstrates that low level elevation of renin release, circulating angiotensin II or aldosterone, or activation of renal sympathetic outflow may alter renal function such that normal natriuretic and diuretic responses to arterial pressure are significantly impeded. Under these circumstances, the maintenance of normal sodium and water excretion requires a significant elevation of arterial pressure. Thus, compromised renal function leads to elevation of arterial pressure to maintain adequate sodium and water balance during periods of increased sodium intake. The resultant chronic elevation of arterial pressure then becomes a compromise that is used by the kidneys to maintain normal extracellular body fluid volumes.
Mental stress increases sympathetic nerve activity during sustained baroreceptor stimulation in humans.
Authors: Anderson E A , Sinkey C A , Mark A L
Published: August 2012

Muscle sympathetic nerve activity (MSNA) in humans is regulated in part by arterial baroreceptors. However, although mental stress increases blood pressure, it also increases MSNA. This suggests that baroreceptor control of MSNA is altered during mental stress. In nine healthy men (age range, 20-26 years), we recorded heart rate, blood pressure, and efferent MSNA (peroneal nerve, microneurography) during a 4-minute mental arithmetic task performed both before and during infusion of phenylephrine sufficient to markedly suppress resting MSNA. Before phenylephrine, mental stress significantly increased mean blood pressure (p less than 0.01), heart rate (p less than 0.01), and MSNA (from 18.5 +/- 3.2 to 24.8 +/- 3.5 bursts/min, p less than 0.001). Phenylephrine infusion increased resting mean blood pressure (from 84.0 +/- 2.6 to 90.0 +/- 2.7 mm Hg, p less than 0.01) and decreased resting heart rate (from 65.6 +/- 1.7 to 55.6 +/- 2.0 beats/min, p less than 0.01). Resting MSNA decreased dramatically during phenylephrine (from 18.5 +/- 3.2 to 3.3 +/- 1.3 bursts/min, p less than 0.01). During phenylephrine, mental stress again significantly (p less than 0.01) increased mean blood pressure, heart rate, and MSNA (from 3.1 +/- 1.4 to 10.9 +/- 1.8 bursts/min). The magnitude of stress-induced increases in MSNA and heart rate were comparable before and during phenylephrine infusion despite the greater elevation in diastolic pressure during stress plus phenylephrine. The present study demonstrates that mental stress produces sympathoexcitatory and pressor responses even during sustained stimulation of arterial baroreceptors.
Effect of stress on diagnosis of hypertension.
Authors: Mancia G , Casadei R , Groppelli A , Parati G , Zanchetti A
Published: August 2012

Blood pressure assessment by a physician elicits an alerting reaction and a pressor response in the patient. The magnitude and time course of this response are described for a large number of hypertensive subjects in whom the assessments were performed during ambulatory intra-arterial blood pressure monitoring. In nearly all of the subjects, the physician's visit was accompanied by blood pressure and heart rate increases that peaked within 4 minutes and then declined. The response was characterized by a relatively high average value; a large between-subject variability; no relation with patient age, baseline hemodynamic values, and responses to laboratory stressors; and no attenuation with multiple repetition of the physician's visit. On the other hand, the increase in blood pressure was considerably less when blood pressure assessment was made by a nurse than when it was made by a physician; in both instances, a 10-minute wait was associated with marked reduction of the initial response. Thus, the stress inherent in usual blood pressure-measuring procedures is responsible for considerable overestimations of patients' blood pressures. There are means by which this can be minimized, although a residual error is likely to remain in most subjects. Whether the stress-devoid blood pressure is a better prognostic index than the stress-related one remains unknown.
Opportunities to improve the cost-effectiveness of treatment for hypertension.
Authors: Stason W B
Published: August 2012

The cost-effectiveness of treatment for hypertension depends on the pretreatment level of blood pressure, age and sex of the patient, presence of other cardiovascular risk factors, long-term control of blood pressure, and the annual costs of treatment. Treatment of very mild hypertension (diastolic blood pressure, 90-94 mm Hg), even if the benefits do exceed the risks, does not appear to be particularly cost-effective. Opportunities to improve the cost-effectiveness of hypertension management lie in 1) avoidance of patient mislabeling by careful documentation of blood pressures on multiple occasions in the office and during usual activities outside the office before the diagnosis is made and treatment is begun; 2) efforts to increase adherence to scheduled visits and medication regimens; 3) attempts to step-down dosages or discontinue medications after periods of good blood pressure control; 4) explicit consideration of costs, as well as benefits, in decisions on the needed frequency of office visits, choice of medications, and use of laboratory tests; and 5) efforts to improve practice efficiency. Future practice guidelines for hypertension management should take these factors into account and should make trade-offs between benefits, risks, and costs explicit for specific types of patients.
Molecular biology of hypertension.
Authors: Krieger J E , Dzau V J
Published: August 2012

Hypertension results from abnormalities of the control systems that normally regulate blood pressure. These control systems include vascular, cardiogenic, renal, neurogenic, and endocrine mechanisms that interact in a complex but integrated manner to achieve blood pressure homeostasis. Multiple endogenous biologically active substances participate in the regulation of these control systems. Evidence suggests that abnormalities of these regulatory mechanisms resulting from altered genetic and environmental interactions play an important role in the pathogenesis of primary hypertension. Once hypertension develops, it tends to be self-perpetuating via amplifying mechanisms mediated by secondary structural changes in the blood vessels, heart, and kidney. These adaptative structural changes amplify and perpetuate hypertension by increasing systemic vascular resistance, enhancing cardiac output, and impairing renal sodium and water excretion. The long-term sequelae of hypertensive structural changes in these end organs are complications of atherosclerotic vascular disease, cardiac hypertrophy and failure, stroke, and renal failure. With the tools of molecular biology, our understanding of the molecular mechanisms underlying these abnormalities has increased enormously and continues to grow at a rapid pace, as illustrated by the discussion that follows. Our review of the molecular biology of hypertension will address systematically four key areas: 1) molecular biology of the control systems, 2) molecular mechanisms of cardiovascular structural changes, 3) genetics of hypertension, and 4) application of transgenic technology in studies of hypertension.
Do primary dysfunctions in neural control of arterial pressure contribute to hypertension?
Authors: Ferrario C M , Averill D B
Published: August 2012

This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject.
Are vascular abnormalities a primary cause or secondary consequence of hypertension?
Authors: Mulvany M J
Published: August 2012

This paper reviews the evidence that the resistance vasculature is altered in hypertension and the role that the vasculature may play in the pathogenesis of the disease. Although functional changes (i.e., increased vascular smooth muscle sensitivity) have been found to be associated with some models of hypertension (e.g., spontaneously hypertensive rat), in human essential hypertension it appears that the abnormalities that predominate in the resistance vasculature are structural in nature. These changes result in an increased media/lumen ratio of the more proximal resistance vessels (i.d. 100-300 microns), and the changes are such that they could account for many of the altered hemodynamic characteristics seen in patients with essential hypertension (e.g., increased minimum vascular resistance, increased pressor response). However, evidence that the abnormal structure of the peripheral vasculature is a prime determinant of blood pressure is still lacking, and much of the available evidence suggests that the altered structure is a secondary adaptation. Nevertheless, the abnormal vascular structure may play an important pathological role concerning the morbid consequences of the hypertensive disease, suggesting that normalization of vascular structure is a desirable aim for antihypertensive treatment. At present it seems that treatment must be continued for long periods, maybe many years, before vascular structure is normalized.
Effects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responses.
Authors: Mombouli J V , Nephtali M , Vanhoutte P M
Published: August 2012

The effects of cilazaprilat were assessed on endothelium-dependent relaxations and contractions in isolated canine arteries. In coronary arteries incubated with indomethacin, cilazaprilat potentiated endothelium-dependent relaxations to bradykinin. In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin. To verify whether this effect was solely due to inhibition of the converting enzyme, the effects of cilazaprilat on responses to a variety of endothelium-dependent vasoactive agents were assessed. Endothelium-dependent relaxations to acetylcholine, thrombin, and vasopressin were not altered significantly by cilazaprilat. However, those induced by ADP and aggregating platelets were enhanced significantly by the compound. Endothelium-dependent relaxations to ADP-beta-S were augmented significantly but to a lesser extent. Furthermore, in the presence of the nitric oxide synthase antagonist NG-nitro-L-arginine, ADP-beta-S still caused small relaxations that were possibly mediated by endothelium-derived hyperpolarizing factor. These relaxations were augmented by cilazaprilat. Thus, the augmentation of purinergic relaxations may involve an increased production of endothelium-derived relaxing factors in addition to the protection of ADP from breakdown. Cilazaprilat did not affect endothelium-dependent contractions to acetylcholine or the calcium ionophore A23187 in canine basilar arteries, previously shown to be mediated by superoxide anions. Thus, cilazaprilat is not a scavenger of superoxide anion. Because this agent potentiates endothelium-dependent relaxations to bradykinin, ADP, and aggregating platelets, the present study suggests that, in addition to the lowering of plasmatic levels of angiotensin II, the antihypertensive and cardioprotective effects of cilazaprilat are mediated through an increased production of endothelium-derived relaxing factors.
Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs.
Authors: Perret F , Mooser V , Hayoz D , Tardy Y , Meister J J , Etienne J D , Farine P A , Marazzi A , Burnier M , Nussberger J
Published: August 2012

A new high-precision ultrasonic device was developed to determine noninvasively arterial compliance as a function of blood pressure. Because of the nonlinear elastic properties of arterial walls, measurements of compliance can be appropriately compared only if obtained over a range of pressures. This apparatus was used to evaluate in a double-blind, parallel fashion the effect of three different antihypertensive drugs and of a placebo on radial artery compliance. Thirty-two normotensive volunteers were randomly allocated to an 8-day, once-a-day oral treatment with either a placebo, 100 mg atenolol, 20 mg nitrendipine, or 20 mg lisinopril. Blood pressure, heart rate, radial artery diameter, and arterial compliance were measured immediately before as well as 6 hours after dosing on the first and last days of the study. On the eighth day of administration, within 6 hours after dosing, lisinopril induced an acute increase in radial artery diameter, from 2.99 +/- 0.06 to 3.28 +/- 0.09 mm (mean +/- SEM, p less than 0.01). The compliance-pressure curve was shifted upward on day 1 (p less than 0.01) as well as on day 8 (p less than 0.05). None of the other drugs induced any significant modification of these parameters. Arterial compliance has a strong nonlinear dependency on intra-arterial pressure and therefore has to be defined as a function of pressure. Antihypertensive drugs acting by different mechanisms may have different effects on the mechanical properties of large arteries.
Evolution of renin.
Authors: Peart W S
Published: August 2012

After the development of blood pressure measurements in humans, the association of high blood pressure with renal disease was established. Injection of extracts of various organs in an attempt to replace their secretions was common in the 19th century, and it was therefore natural for Tigerstedt and Bergman to investigate the effects of renal extracts. In this way, they discovered renin. This paper covers the methods by which its mode of action was uncovered, as well as its relation to renal ischemia and hypertension.
Adrenergic pharmacology in rats harboring pheochromocytoma.
Authors: Hoffman B B
Published: August 2012

Hypertension and cardiomyopathy are prominent findings in both humans and rats harboring pheochromocytomas, tumors that secrete enormous quantities of catecholamines in an unregulated fashion. We used New England Deaconess Hospital rats harboring pheochromocytomas to investigate the effects of chronic exposure to high concentrations of catecholamines on desensitization of alpha- and beta-adrenergic receptor-mediated responses activated by catecholamines. In addition, rats harboring pheochromocytomas provide a useful model to investigate catecholamine-induced hypertension and cardiomyopathy.
Pathophysiology of the vasculature in hypertension.
Authors: Bohr D F , Dominiczak A F , Webb R C
Published: August 2012

The vessel wall is thicker in hypertension. Folkow demonstrated that adaptive structural changes occur in vessels in response to the increased wall stress of hypertension. Because the vessel wall thickens and encroaches on the lumen, the adaptive change results in an elevated vascular resistance. It also exaggerates the vasoconstrictor effects of vascular smooth muscle contraction, thereby increasing vascular reactivity to physiologically occurring vasoactive agents. As solid as this information may be, important unanswered questions still remain related to the question "What makes the pressure go up in the first place?" In this brief review, we have examined possible culprits both in the area of extrinsic vascular regulatory systems and in that of intrinsic changes in the vascular smooth muscle cell. Interesting newly described vasoactive agents currently are being evaluated. On the other hand, generalized intrinsic abnormalities in the cell membrane are well documented in hypertension. Many individual transport systems display this abnormality, suggesting that the primary defect may be in the lipid bilayer that influences the function of all integral protein transport systems. Abnormalities also have been found in the cells' signal transduction systems, whereas the energy metabolism and contractile protein system are essentially normal. Functional abnormalities of the vascular smooth muscle cell in hypertension must explain both its increased contraction and its increased growth. It is likely that the same functional abnormality may explain both of these changes.
Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation.
Authors: Shepherd J T , Katusić Z S
Published: August 2012

Evidence continues to accumulate on the importance of paracrine substances formed in the vascular endothelium in the regulation of the vascular system. Those that relax the underlying smooth muscle include nitric oxide, prostacyclin, and an unidentified hyperpolarizing factor; those causing contraction include angiotensin II, endothelin, oxygen-derived free radicals, prostacyclin H2, and thromboxane A2. Determination of the mechanisms governing the formation and release of these substances in different blood vessels of the same species and in different species as well as the maintenance of the balance between them is important for understanding their role in normal circumstances and in diseases of the blood vessels. In this article, we will summarize the current understanding of the role of endothelium-derived relaxing factors and discuss the possibility that endothelial dysfunction may play a primary as well as a secondary role in the pathogenesis of primary hypertension. As a consequence of this dysfunction, substances formed in the endothelial cells at the sites of the arterial baroreceptors could lead to their resetting, resulting in less inhibition of the vasomotor centers, enhanced neurohumoral activity, and a consequential increase in systemic vascular resistance. This increase could be enhanced by a predominant action of endothelium-derived contracting factors in the resistance vessels. Proliferation of the vascular smooth muscle would follow, because of the mitogenic action of some of these factors and other growth promotors. By these mechanisms, the endothelium may participate in the polygenic dysfunction characteristic of primary hypertension, not only in initiating the increase in arterial blood pressure, but also in sustaining it.
Endothelium-derived vasoactive factors: II. Endothelium-dependent contraction.
Authors: Katusić Z S , Shepherd J T
Published: August 2012

Endothelial cells may produce and release vasoconstrictor substances in response to a number of agents and physical stimuli. In this brief review, current understanding of the mechanisms of endothelium-dependent contractions will be discussed. Cyclooxygenase products of arachidonic acid metabolism including thromboxane A2, prostaglandin H2, superoxide anions, vasoconstrictor peptide endothelin-1, and unidentified factor released from endothelium by hypoxia may mediate these contractions. The physiological role of endothelium-dependent contractions in regulation of the cardiovascular system is unknown. Existing evidence supports the concept that contracting factors may become important regulators of vascular tone under pathological conditions. We speculated about the possible importance of endothelium-dependent contractions for venous graft function, development of vasospasm, increased vascular resistance in hypertension, and vascular complications in diabetes.
Hyperamylinemia, hyperinsulinemia, and insulin resistance in genetically obese LA/N-cp rats.
Authors: Huang H J , Young A A , Koda J E , Tulp O L , Johnson M J , Cooper G J
Published: August 2012

The experimental evidence supporting a direct role for hyperinsulinemia as a cause of insulin resistance remains equivocal. Amylin, an islet beta-cell peptide cosecreted with insulin in response to nutrient stimuli, causes insulin resistance when infused into intact animals or applied to isolated skeletal muscles. We compared measures of amylin and insulin gene expression between control and genetically obese, insulin-resistant Lister Albany/NIH-(LA/N-cp) rats. Pancreatic amylin messenger RNA levels were increased 7.8 +/- 0.7-fold (mean +/- SEM), and plasma amylin-like immunoreactive material was increased 10.9 +/- 1.1-fold (LA/N-lean, 14 +/- 4 pM; LA/N-cp, 153 +/- 16 pM; p less than 0.0001) in obese rats. Pancreatic insulin I mRNA levels were increased 7.4 +/- 0.5-fold, and plasma insulin levels 20.0 +/- 5.0-fold, in these rats (LA/N-lean, 308 +/- 84 pM; LA/N-cp 6,120 +/- 1,540 pM; p less than 0.0001). The EC50 for insulin-stimulated incorporation of glucose into glycogen was about fourfold higher in muscles isolated from obese rats. The present results, coupled with previous observations, support the hypothesis that hyperamylinemia, rather than hyperinsulinemia per se, could have directly caused the insulin resistance in the obese LA/N-cp rats. Hyperamylinemia needs to be considered in future experimental studies probing the relation between hyperinsulinemia and insulin resistance.
Pressure natriuresis. Role of renal interstitial hydrostatic pressure.
Authors: Granger J P
Published: August 2012

The kidneys play a major role in the long-term regulation of extracellular fluid volume and arterial pressure. A central component of the feedback system for long-term control of arterial pressure is the pressure-natriuresis mechanism, whereby increases in renal perfusion pressure lead to decreases in sodium reabsorption and increases in sodium excretion. The specific intrarenal mechanism for the decrease in tubular reabsorption in response to increases in renal perfusion pressure appears to be related to increases in renal interstitial hydrostatic pressure (RIHP). Increases in renal perfusion pressure are associated with significant increases in RIHP. The mechanism whereby RIHP increases in the absence of discernible changes in whole kidney renal blood flow and peritubular capillary hydrostatic and/or oncotic pressures may be related to alterations in renal medullary hemodynamics. Several lines of investigation support an important quantitative role for RIHP in mediating pressure natriuresis. Preventing RIHP from increasing in response to increases in renal perfusion pressure markedly attenuates pressure natriuresis. Furthermore, direct increases in RIHP, comparable to increases measured in response to increases in renal perfusion pressure, have been shown to significantly decrease tubular reabsorption of sodium in the proximal tubule and increase sodium excretion. The exact mechanism whereby RIHP influences tubular reabsorption is unknown but may be related to alterations in tight junctional permeability to sodium in proximal tubules and/or release of renal autacoids such as prostaglandins.
Blunted natriuretic response to an acute sodium load in obese hypertensive dogs.
Authors: West D B , Wehberg K E , Kieswetter K , Granger J P
Published: August 2012

Several studies support the premise that there is a strong relation between obesity and high blood pressure. Although the mechanism for obesity-related hypertension has not yet been fully elucidated, recent studies have suggested that abnormalities in renal sodium handling may be involved in the pathogenesis of obesity-induced hypertension. The purpose of the present study was to determine the effects of an acute saline load on renal excretory function in dogs with obesity-induced hypertension and in normotensive lean dogs. Experiments were performed in two groups of conscious, chronically instrumented dogs. One group of dogs (obese) was fed a high-fat diet for 5-6 weeks, and the other group (lean) ate a normal diet. The body weight of the obese dog group (26.3 +/- 0.7 kg) was 45% higher than the lean dog group (18.1 +/- 0.3 kg). Mean arterial pressure averaged 126 +/- 2 mm Hg in the obese dogs and 100 +/- 1 mm Hg in the lean dogs. The lean dogs had an average heart rate of 104 +/- 7 beats per minute, whereas the obese dogs averaged 134 +/- 8 beats per minute. Plasma renin activity was also significantly higher in the obese dogs. Both groups of dogs were given 135 meq sodium chloride over 60 minutes via an intravenous infusion of isotonic saline. Sodium and water excretion increased significantly in response to the acute saline load. However, the natriuresis and diuresis was markedly attenuated in the obese hypertensive dogs. During the first 40 minutes of saline loading, the increase in sodium and water excretion was 50-70% lower in the obese hypertensive dogs. The results of the present study indicate that obese hypertensive dogs have a reduced capability to excrete an acute sodium load. This abnormality in renal sodium handling may play a role in the pathogenesis of obesity-induced hypertension.
Antihypertensive effect of gamma-linolenic acid in spontaneously hypertensive rats.
Authors: St Louis C , Lee R M , Rosenfeld J , Fargas-Babjak A
Published: August 2012

The effects of chronic treatments of adult (aged 16-17 weeks) spontaneously hypertensive rats (SHRs) with different doses of gamma-linolenic acid (GLA) on blood pressure, heart rate, and body weight were studied. Twice-daily injection of SHRs with GLA lowered systolic blood pressure from 175 +/- 4 to 145 +/- 4 mm Hg within 1 week; systolic blood pressure in all three treated groups became stabilized in the normotensive range after 2 weeks of treatment. Control SHRs injected with olive oil showed only a transient decrease in systolic blood pressure on the third day. Heart rate and body weight were not affected by GLA treatment. Withdrawal of GLA treatment resulted in a rapid rise in systolic blood pressure within 1 day from 140 +/- 3 to 165 +/- 3 mm Hg, and it stabilized after 1 week at 191 +/- 5 mm Hg in the three experimental groups. A rapid increase in systolic blood pressure from 175 +/- 5 to 203 +/- 5 mm Hg was also observed in the control group treated with olive oil 1 day after the withdrawal of the treatment. Addition of aspirin (3 mg/kg) with the GLA treatment in olive oil abolished the antihypertensive effect of GLA. In contrast, once-daily treatment with GLA also lowered systolic blood pressure of the SHR, but blood pressure was still in the hypertensive range (170 +/- 6 mm Hg). Systolic blood pressure of control SHRs treated with olive oil was not affected. Plasma from untreated SHRs contained a small amount of GLA. One hour after the injection, the plasma level of GLA increased. We conclude that GLA when given twice daily is an effective antihypertensive agent in the SHR.
Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose-finding pilot study.
Authors: Voto L S , Lapidus A M , Catuzzi P , Uranga Imaz F , Zin C , Margulies M
Published: August 2012

The antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache).
Pressure-induced constriction of the afferent arteriole of spontaneously hypertensive rats.
Authors: Ito S , Juncos L A , Carretero O A
Published: August 2012

In uncomplicated essential hypertension, renal blood flow, glomerular filtration rate, and glomerular capillary pressure are within the normal range despite elevated renal perfusion pressure, suggesting abnormally high resistance of the preglomerular vessels. Among various preglomerular vascular segments, the afferent arteriole (Af-Art) is thought to be the site responsible for most resistance. However, little is known about the vascular reactivity of the Af-Art or its alteration in hypertension. In this study, we tested the hypothesis that pressure-induced constriction is exaggerated in Af-Arts from spontaneously hypertensive rats (SHRs). Single Af-Arts were microdissected from kidneys of SHRs and normotensive control Wistar-Kyoto (WKY) rats and were microperfused in vitro. When pressure in the Af-Art was increased stepwise from 20 to 80 mm Hg, luminal diameter increased similarly in both WKY and SHR Af-Arts (from 10.0 +/- 0.8 to 18.6 +/- 1.3 microns and from 10.1 +/- 1.2 to 16.9 +/- 1.5 microns, respectively). However, when pressure was further increased to 140 mm Hg, the diameter remained unchanged in WKY Af-Arts (19.2 +/- 1.9 microns), whereas it decreased significantly to 11.1 +/- 0.9 microns in those from SHRs. We conclude that pressure-induced constriction is exaggerated in SHR Af-Arts, which may contribute to the development and maintenance of hypertension.
Identification of cardiovascular neurons in the rostral ventromedial medulla in anesthetized rats.
Authors: Varner K J , Rutherford D S , Vasquez E C , Brody M J
Published: August 2012

Recent studies have identified a region in the rostral ventromedial medulla (RVMM) of rats that appears to be involved in cardiovascular function. Since these studies used either microinjection of lidocaine or electrical stimulation, the exact contribution of intrinsic neurons as opposed to fibers of passage could not be determined. The present study was performed to map the location of neurons in RVMM from which changes in mean arterial pressure could be elicited by the microinjection of the excitatory amino acid analogue N-methyl-D-aspartic acid (NMDA) (20 ng/50 nl), which selectively activates cell bodies in barbiturate-anesthetized rats. Microinjection of NMDA into RVMM most often (53%) elicited pressor responses (31 +/- 7 mm Hg). On the basis of these responses, RVMM was determined to encompass a large portion of the nucleus gigantocellularis 0.5-1.5 mm lateral to the midline, 0.5-3.5 mm above the ventral surface, and extending from the rostral to the caudal pole of the facial nucleus. Depressor responses (-21 +/- 3 mm Hg) were found at all levels of RVMM but were most concentrated and of the largest magnitude in the rostral and caudal poles of RVMM. Microinjection of the inhibitory neurotransmitter glycine (500 mM) was used to determine whether neurons in RVMM were contributing to the maintenance of arterial pressure. Microinjection of glycine decreased arterial pressure (-15 +/- 2 mm Hg) throughout most of RVMM. Unexpectedly, increases in mean arterial pressure (24 +/- 3 mm Hg) were elicited by microinjection of glycine into the same region in RVMM in which NMDA most frequently elicited pressor responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Familial aggregation of arterial blood pressure and possible genetic influence.
Authors: Brandão A P , Brandão A A , Araújo E M , Oliveira R C
Published: August 2012

The aggregation of arterial blood pressure, weight, and height were compared between family members of children and adolescents with blood pressure percentiles at or above 95 (group 1) and at or below 50 (group 2). Weight, height, and systolic and diastolic blood pressures were significantly higher in siblings and target individuals of group 1 (p less than 0.001). Weight and systolic and diastolic blood pressures were significantly higher in mothers of group 1 (p less than 0.001). Covariant analysis comparing the average systolic and diastolic blood pressures of both groups controlled by age, age and weight, and age and Quetelet index revealed that the arterial blood pressure of mothers, siblings, and target individuals remained higher in group 1 (p less than 0.05 to p less than 0.001). These observations show a strong familial aggregation of arterial blood pressure not dependent only on physical development and also raise the question of a genetic basis as a possible mechanism of systemic arterial hypertension.
Effect of bradykinin on isolated mesenteric arteries of the rat.
Authors: Salgado M C , Caldo H , Rodrigues M C
Published: August 2012

Bradykinin is a potent vasodilator peptide; however, its half-life in vivo is very short because of various plasma and tissue peptidases that hydrolyze bradykinin to inactive fragments. We studied the role of kininase II (angiotensin converting enzyme) and neutral endopeptidase 24.11 (enkephalinase) in the catabolism of bradykinin in vascular tissue by determining the effect of inhibitors of kininase II (captopril) and of endopeptidase 24.11 (phosphoramidon) on the action of bradykinin on rat isolated mesenteric arteries. Because bradykinin may induce prostaglandin formation and release, we also studied the effect of a cyclooxygenase inhibitor, indomethacin, on the action of bradykinin. The mesenteric bed was isolated from rats (250-300 g) with rats under either anesthesia and was perfused with Krebs' solution (4 ml/min) containing phenylephrine (0.5-1.0 microgram/ml) to produce a mean perfusion pressure of 120-130 mm Hg. Bradykinin (2.5-40.0 ng), injected as a bolus, produced a dose-dependent decrease in perfusion pressure. In the presence of indomethacin (1.0 microgram/ml), the amplitude of the vasodilator responses to bradykinin was not significantly affected, although the duration of the responses was increased approximately two to four times. In the presence of captopril (1.0 microgram/ml), bradykinin elicited either a vasodilator or a biphasic effect. The vasodilator effect was greatly potentiated by captopril, whereas the duration of the response was unchanged when compared with control experiments. When present, the pressor responses were also dose related. In the presence of indomethacin plus captopril, bradykinin produced only a fall in perfusion pressure that lasted five to six times longer than without any treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats.
Authors: Wang Y X , Gavras I , Wierzba T , Lammek B , Gavras H
Published: August 2012

We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with NG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n = 8), mean blood pressure increased by 16.2 +/- 2.6 mm Hg, and heart rate decreased by 54.3 +/- 16.7 beats per minute. In comparison with rats injected with 5% dextrose (n = 14), cardiac index was lower by 35.6% (p less than 0.01), and total peripheral vascular resistance was higher by 51.6% (p less than 0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (p less than 0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 micrograms/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2% (p less than 0.01) and vascular resistance increasing by 75.3% (p less than 0.01) compared with changes produced by LNMMA alone.(ABSTRACT TRUNCATED AT 250 WORDS)