bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial function in human coronary arteries in vivo. Focus on hypercholesterolemia.
Authors: Drexler H , Zeiher A M
Published: August 2012

To examine whether and to what extent hypercholesterolemia may affect the vasoactive role of the endothelium before the onset of angiographically visible atherosclerosis in the coronary circulation, we studied normal subjects (group 1, n = 11), individuals with elevated low density lipoprotein plasma values but angiographically smooth coronary arteries (group 2, n = 8), and patients with hypercholesterolemia and minimal disease of the vessel under study (group 3, n = 8). Coronary vasomotor function was evaluated by three interventions: subselective intracoronary infusion of acetylcholine (0.036, 0.36, and 3.6 micrograms/min) with a 3F Doppler catheter in the left anterior descending artery, 0.3 mg intracoronary nitroglycerin ("endothelium-independent"), and increase in blood flow (assessment of flow-dependent, endothelium-mediated coronary dilation). In group 1, all interventions caused coronary dilation of the left anterior descending artery as assessed by automatic quantification of digitized cineframes. However, in group 2, acetylcholine elicited substantial coronary vasoconstriction, and the vasodilator response to nitroglycerin and to increases in flow (flow-dependent dilation) was preserved. In group 3, the acetylcholine-induced coronary vasoconstriction was even more pronounced, and the flow-dependent dilation was impaired (+5.1 +/- 1% versus +10.5 +/- 1.1% [group 1], p less than 0.05). The coronary flow reserve (derived from Doppler flow velocity measurements) in response to papaverine was not significantly different in normal and hypercholesterolemic individuals (groups 2 and 3). However, the increase in coronary flow exerted by acetylcholine was substantially depressed in patients with hypercholesterolemia (groups 2 and 3) as compared with normal individuals (+48 +/- 8.3% and +49 +/- 25% versus +220 +/- 28.5%, respectively, p less than 0.01). Thus, hypercholesterolemia elicits endothelial dysfunction in coronary conduit and resistance vessels in humans that precedes angiographically visible atherosclerotic lesions in large coronary arteries. Conceivably, these vascular alterations contribute to increased coronary vasomotor tone within the coronary circulation and may predispose these patients to myocardial ischemia.
Angiotensin I and II. Some early observations made at the Cleveland Clinic Foundation and recent discoveries relative to angiotensin II formation in human heart.
Authors: Bumpus F M
Published: August 2012

The renin-angiotensin system originally was thought to be responsible for only renovascular hypertension, but the development and use of various inhibitors of this system have produced much evidence for its participation in many forms of hypertensive disease. Tissue renin-angiotensin system also may play a major role in blood pressure control. Chronic clinical as well as animal use of converting enzyme inhibitors results in levels of angiotensin II that are equivalent to those found in the normotensive state and higher than those found in the very acute phase of treatment. The source of this conversion possibly may be due to enzymes unrelated to angiotensin converting enzyme. One such enzyme is a very highly specific serine protease isolated from human cardiac tissue. This enzyme exists in human ventricular tissue at levels four to five times that of angiotensin converting enzyme. During chronic treatment of patients with heart failure, angiotensin I levels become high, and heart tissue levels of angiotensin II may become elevated because of the conversion to angiotensin II by this serine protease. This conversion in turn may possibly increase inotropy of the heart, whereas the peripheral resistance remains low because of the reduction of angiotensin II in the circulation.
Angiotensin-(1-7): a new hormone of the angiotensin system.
Authors: Ferrario C M , Brosnihan K B , Diz D I , Jaiswal N , Khosla M C , Milsted A , Tallant E A
Published: August 2012

We provide a new foundation for an alternative interpretation of the biochemical physiology of the brain and other tissue angiotensin systems on the basis of research done in our laboratory. This perspective is prompted by the discovery that angiotensin-(1-7) has cellular functions that differ from those established for angiotensin II. Although angiotensin-(1-7) is not an agonist in terms of activating vasoconstriction, stimulating thirst, or promoting aldosterone release, the heptapeptide caused neuronal excitation and vasopressin release with a potency similar to that found with angiotensin II. Furthermore, angiotensin-(1-7) enhances the production of prostanoids by a receptor-mediated event that causes no associated rise in intracellular Ca2+. These actions of angiotensin-(1-7) provide a new understanding of the heterogeneous functions of angiotensin peptides as modulators of a wide range of regulatory functions in mammals.
Functional derangements in the regulation of aldosterone secretion in hypertension.
Authors: Williams G H , Hollenberg N K
Published: August 2012

Excess production of aldosterone secondary to an adrenal tumor or bilateral hyperplasia is a known, but infrequent, cause of hypertension. A more frequent adrenal abnormality, observed in 30-40% of hypertensive patients, is a functional derangement in aldosterone secretion. Two such conditions have been described: low renin essential hypertension and non-modulating essential hypertension. Both have in common 1) an abnormality in the interaction of angiotensin II (Ang II) with the adrenal and 2) sodium sensitivity of the blood pressure. However, the pathophysiological mechanisms for the sodium sensitivity and hypertension are different. In normal subjects, the response of the adrenal glomerulosa cell to Ang II varies with the level of sodium intake, with sodium restriction enhancing the response. In one group of hypertensive patients with low plasma renin levels, the normally reduced aldosterone responses to Ang II on the high salt diet do not occur. Thus, these individuals have an enhanced adrenal response to Ang II under circumstances in which it should be reduced, thereby leading to lower renin levels and a tendency toward sodium retention. The second group has the opposite defect; that is, on a low sodium diet, they have a reduced adrenal response to Ang II. This results in a normal or high plasma renin level. The sodium sensitivity of their blood pressure arises not from the adrenal abnormality but from the associated defect in sodium-dependent, Ang II-mediated changes in renal blood flow. Thus, on a high salt diet, these patients, who are termed "non-modulators," fail to increase renal blood flow, thereby leading to a sodium-retaining state.(ABSTRACT TRUNCATED AT 250 WORDS)
Arachidonate metabolites and kinins in blood pressure regulation.
Authors: McGiff J C , Carroll M A , Escalante B
Published: August 2012

Arachidonic acid (AA) can be metabolized to an array of products affecting biological mechanisms such as those governing vascular reactivity and transport function. Metabolism of AA by cyclooxygenase in the nephron is discretely localized and is overshadowed in some nephron segments by a considerable capacity to generate P-450 AA metabolites. The synthesis of renal P-450 AA products is increased in hypertension. AA metabolites participate in fluid and electrolyte homeostasis and regulation of tissue blood flow and act as modulators of pressor systems. In addition, eicosanoids either augment or mediate the vasodilator-diuretic actions of the kallikrein-kinin system.
Stretch-secretion coupling in atrial cardiocytes. Dissociation between atrial natriuretic factor release and mechanical activity.
Authors: Kuroski-de Bold M L , de Bold A J
Published: August 2012

We investigated possible relations between excitation-contraction coupling and atrial natriuretic factor (ANF) release in rat atrial muscle using the isolated perifused atria preparation. To this purpose, the extracellular ionic environment was manipulated by replacement of Ca2+ with the polyvalent cations Ba2+, Sr2+, and La3+. Intracellular Ca2+ was altered by treatment with caffeine and ryanodine and by chemical (49 mM K+) depolarization. Replacement of Ca2+ with Ba2+ or Sr2+ abolished atrial spontaneous mechanical activity but did not prevent ANF release. Chemical depolarization also abolished spontaneous mechanical activity and significantly reduced ANF release in Ca(2+)-free media and in 0.625 mM extracellular Ca2+ but had no effect in the presence of 1.25 or 2.5 mM Ca2+, suggesting that changes in cytosolic Ca2+ levels do not affect ANF release in media containing Ca2+ in the physiological concentration range. The kinetics of ANF release observed during caffeine (10(-6) to 10(-2) M) treatment was similar to that seen in atrial preparations without treatment. At 10(-2) M, caffeine induced an increase in atrial beating rate and resting tension. Ryanodine (10(-4) M) pretreatment reduced stretch-induced ANF release by an average 34%, in addition to inhibiting tension development and beating. These findings clearly show marked differences between atrial cardiocytes and most other endocrine cells in terms of the effect of specific changes in the ionic environment on the secretory response; they also support the view that basal ANF release from atrial cardiocytes is not dependent on contractile atrial activity or Ca2+. In fact, Ca2+ appears to tonically inhibit the rate of basal ANF release. We conclude that, although indispensable for excitation-contraction coupling, intracellular Ca2+ transients by influx or from intracellular stores are not essential for basal ANF release. However, a ryanodine-sensitive compartment appears to be partly responsible for the increased ANF output after muscle stretch.
Roles of sodium, potassium, calcium, and natriuretic factors in hypertension.
Authors: Haddy F J
Published: August 2012

This review first summarizes evidence from animals and humans for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for its role is strongest in those subjects with impaired ability to excrete sodium because of organic renal disease or mineralocorticoid excess. Here, restriction of dietary sodium promptly lowers pressure. Its role in the genesis of essential hypertension is more controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep pressure under control. Next, the mechanism of the pressure response to dietary sodium chloride is considered, with emphasis on potassium depletion and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic peptide. The evidence for a primary role for dietary potassium in the genesis of hypertension then is summarized; certain subsets of subjects with a high incidence of hypertension also have a lower potassium intake. Some investigators have found that dietary potassium supplementation lowers pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+,K(+)-ATPase in vascular smooth muscle and adrenergic nerve terminals. After the role of dietary calcium is discussed, practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension are considered. The review concludes with comments on their possible roles in the prevention of hypertension.
The heart in hypertension: a 1991 overview.
Authors: Frohlich E D
Published: August 2012

Left ventricular hypertrophy may be considered the result of an interaction of a myriad of factors, including hemodynamic overload; age, race, and gender of the patient; the stage of hypertensive disease; and other coexisting diseases. This concept is similar to the multifactorial "mosaic of hypertension" described by Page. In addition, the increased left ventricular mass in hypertension may reflect the disposition of collagen tissue and the participation of a myriad of myocytic growth factors, as well as drug therapy. The resultant left ventricular hypertrophy confers increased cardiovascular risk that is independent of the height of arterial pressure. The mechanisms that account for that risk are not yet well understood but include reduced adaptive myocardial reserve, enhanced predisposition to cardiac dysrhythmias and cardiac failure, accelerated atherosclerosis, and reduced (absolute and relative) coronary flow and flow reserve, as well as other possibilities. At present much work is directed to the demonstration of pharmacological reversal of hypertrophy. However, even with that demonstration of reduced cardiac mass with therapy, it will be necessary to show improved risk at the reduced mass that is independent of the reduction of arterial pressure as well as of the effects of those drugs on cardiac rhythm, flow, metabolism, and direct effects on the cardiac myocyte itself.
Central nervous system and the pathogenesis of hypertension. Sites and mechanisms.
Authors: Brody M J , Varner K J , Vasquez E C , Lewis S J
Published: August 2012

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.
Effects of antihypertensive therapy on insulin resistance.
Authors: Kaplan N M
Published: August 2012

In view of the likely prohypertensive effects of hyperinsulinemia and the presence of insulin resistance in primary hypertension, the effects of various antihypertensive therapies on insulin sensitivity need to be identified. The evidence strongly supports major beneficial effects of weight reduction and aerobic exercise. Deleterious effects have been shown for diuretics and most beta-blockers, whereas probable beneficial effects have been seen with alpha-blockers, one angiotensin converting enzyme inhibitor, and various calcium entry blockers. Improvement of insulin sensitivity and reduction of plasma insulin levels are desirable attributes of antihypertensive therapy that should be more carefully considered in the future.
Obesity hypertension. Converting enzyme inhibitors and calcium antagonists.
Authors: Frohlich E D
Published: August 2012

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.
Antihypertensive therapy and cardiovascular risk. Are all antihypertensives equal?
Authors: Giles T D
Published: August 2012

The lack of success of antihypertensive drug therapy in decreasing cardiovascular events has caused close examination of the influence of antihypertensive drugs on cardiac risk factors. Striking differences exist in the pharmacological profiles of antihypertensive drug classes and subclasses as well as in the influences of the drugs on electrolyte, lipid, and glucose metabolism. Differences also exist in the effects of the drugs on left ventricular hypertrophy. These differences in the effects of antihypertensive drugs on cardiac risk factors may assist in explaining the lack of a favorable effect on cardiovascular events in previous clinical trials. However, prospective trials are necessary to demonstrate that treatment of hypertension with drugs that have a more favorable effect on cardiac risk factors will reduce cardiac events (i.e., myocardial infarction, heart failure, and sudden death).
Sympathetic neural control of the kidney in hypertension.
Authors: DiBona G F
Published: August 2012

Efferent renal sympathetic nerve activity is elevated in human essential hypertension as well as in several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow, the glomerular filtration rate, renal tubular sodium and water reabsorption, and the renin secretion rate, which are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of efferent renal sympathetic nerve activity, two environmental factors, a high dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in efferent renal sympathetic nerve activity and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.
Obesity, the sympathetic nervous system, and essential hypertension.
Authors: Tuck M L
Published: August 2012

There is ample evidence that the sympathetic nervous system is important in the etiology of essential hypertension. Plasma catecholamines such as norepinephrine and epinephrine are the most common indexes of sympathetic function used in studies of essential hypertension. Plasma norepinephrine is higher in young essential hypertensive patients than in normotensive subjects. Other methods to examine sympathetic activity, such as blood pressure response to sympatholytic agents, measurement of regional sympathetic activity, vascular reactivity to sympathetic agonists, power spectral analysis, and microneurography, have all provided further evidence for enhanced sympathetic activity in essential hypertension, especially in younger subjects. Certain groups that make up a substantial part of the essential hypertensive population, such as obese subjects, have heightened sympathetic activity that could contribute to hypertension. Plasma norepinephrine levels are significantly higher in obese compared with nonobese subjects, and the remarkable fall in blood pressure with weight loss in obese subjects is correlated with reductions in plasma norepinephrine. Antihypertensive agents have variable effects on sympathetic activity; some agents (diuretics and direct vasodilators) have elevating effects, some agents (centrally acting agents and alpha-antagonists) have lowering effects, and others (converting enzyme inhibitors, calcium blockers, and beta-blockers) have mixed effects. Tailoring therapy toward agents that reduce sympathetic activity for specific groups perceived as having neurogenic hypertension, such as obese subjects, is a goal yet to be attained.
Chemical renal medullectomy and arterial pressure response to sinoaortic denervation.
Authors: Beloni S N , Silva-Costa R , Machado B H , Salgado H C
Published: August 2012

We investigated in conscious Wistar-Kyoto rats the effect of chemical renal medullectomy on the responses of mean arterial pressure, arterial pressure lability, and heart rate to sinoaortic deafferentation (SAD). Chemical medullectomy was obtained by the intravenous administration of 2-bromoethylamine hydrobromide (2-BEA) 2-3 weeks before SAD or sham SAD. Chemically medullectomized rats were compared with control rats treated with saline. In control rats, the increase in mean arterial pressure elicited by SAD was not significantly greater than that produced by sham SAD. In medullectomized rats, SAD significantly increased mean arterial pressure compared with sham SAD. No direct relation was observed between the response of mean arterial pressure to SAD and the grade (1, 2, or 3) of lesion of the renal papilla. In control rats, SAD increased significantly arterial pressure lability. Chemical medullectomy did not affect basal lability or the increased lability after SAD. No direct relation was observed between increased arterial pressure lability due to SAD and the grade of lesion of the renal papilla. SAD produced a conspicuous tachycardia in control rats. Chemical medullectomy did not affect basal heart rate or the tachycardia produced by SAD. No direct relation was observed between the extent of this tachycardia and the grade of lesion of the renal papilla. These data indicate that lesions of the renal papilla lead to a significant increase in mean arterial pressure after SAD, without affecting basal pressure or heart rate. In addition, SAD per se did not increase significantly the mean arterial pressure in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal effects of angiotensin II inhibition during increases in renal venous pressure.
Authors: Fiksen-Olsen M J , Strick D M , Hawley H , Romero J C
Published: August 2012

Increases in renal venous pressure have been shown to consistently increase renal interstitial pressure; however, not until renal interstitial pressure is increased threefold is a natriuresis noted in normal animals. Since the intrarenal angiotensin II (Ang II) concentration has been postulated to increase with increasing renal venous pressure, the antinatriuretic action of Ang II could override the natriuretic effect of increased renal interstitial pressure. Therefore, the role of Ang II in the natriuretic response to increased renal venous pressure was examined in 10 pentobarbital-anesthetized dogs. Mean arterial pressure, renal blood flow, renal interstitial pressure, glomerular filtration rate, urinary sodium excretion, plasma renin activity, and prostaglandin E2 excretion were measured at renal venous pressures of 3, 15, and 30 mm Hg. The measurements were repeated after the administration of captopril (1 mg/kg i.v. bolus, n = 5) or [Sar1,Ile8]Ang II (50 micrograms/kg i.v. bolus + 50 micrograms/kg/hr infusion, n = 5). Under control conditions, mean arterial pressure, renal blood flow, plasma renin activity, and prostaglandin E2 excretion remained unchanged when renal venous pressure was increased. The elevations in renal venous pressure increased renal interstitial pressure from 7 +/- 2 to 12 +/- 2 and 22 +/- 4 mm Hg, while sodium excretion remained unchanged until renal venous pressure was 30 mm Hg. In the captopril-treated group, increasing renal venous pressure increased renal interstitial pressure as under control conditions; however, sodium excretion (23 +/- 4, 19 +/- 4, and 27 +/- 6 mueq/min) was not significantly increased even at the highest renal venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats.
Authors: Bendhack L M , Sharma R V , Bhalla R C
Published: August 2012

The hypothesis that signal transduction mediated by platelet-derived growth factor (PDGF) and angiotensin II (Ang II) is altered in vascular smooth muscle (VSM) cells from the spontaneously hypertensive rat (SHR) was tested by measuring changes in the cytosolic free calcium concentration ([Ca2+]i). [Ca2+]i was measured in cultured aortic smooth muscle cells from SHRs and Wistar-Kyoto (WKY) normotensive rats using fura-2 as a calcium indicator and a microscopic digital image analysis system. Activation of cells with Ang II resulted in a prompt though transient rise in [Ca2+]i; the maximum increase was observed after 10-30-second intervals. On the other hand, activation of cells with PDGF BB produced an increase in [Ca2+]i with a 40-60-second lag period; the maximum increase was observed 2-4 minutes after the addition of PDGF. PDGF-stimulated increases in [Ca2+]i were markedly inhibited by the addition of the calcium channel antagonist verapamil (100 microM) as well as by removal of calcium from the extracellular bathing medium. However, Ang II-stimulated [Ca2+]i was not significantly affected by the addition of verapamil or by removal of extracellular calcium. These results would indicate that PDGF-mediated increases in [Ca2+]i in VSM cells are predominantly via Ca2+ influx, whereas Ang II-mediated increases are due to calcium release from intracellular pools. Basal and PDGF- and Ang II-stimulated increases in [Ca2+]i were significantly greater (p less than 0.05) in SHR VSM cells compared with WKY cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats.
Authors: Vasquez E C , Lewis S J , Varner K J , Brody M J
Published: August 2012

We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +/- 7 versus 173 +/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +/- 6 versus 167 +/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +/- 13 beats per minute) but a tachycardia in sham rats (+33 +/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats.
Effect of selective denervation of baroreceptors on pulmonary ventilation and arterial pressure lability in rat.
Authors: Mauad H , Glass M L , Machado B H
Published: August 2012

Earlier studies report that sinoaortic baroreceptor denervation (SAD) in rats causes moderate elevation of mean arterial pressure along with a marked increase of arterial pressure lability (APL). In this context, we studied the effects of selective aortic denervation (AD) or selective carotid denervation (CD) on the regulation of blood pressure. In addition, we evaluated the effects of selective or total baroreceptor denervation on pulmonary ventilation and ventilation-related changes of arterial pressure. Mean arterial pressure was evaluated by computer-assisted techniques, and ventilation was measured by whole body plethysmography on conscious freely moving rats. With this approach, equal increases of mean arterial pressure were obtained for rats that had undergone AD, CD, and SAD. The APL was higher in SAD rats than in selectively denervated rats. CD and AD rats had an elevated APL relative to sham-operated animals, and its increase was approximately equal for the two selectively denervated groups. Total as well as selective denervation had relatively small effects on ventilation and on the general pattern of breathing. In all groups, this pattern consisted of regular ventilation, periodically interrupted by single deeper breaths. In SAD, AD, and CD animals, these larger tidal volumes were associated with marked transient reductions of mean arterial pressure, whereas small decreases of pressure occurred in sham-operated rats. The results indicate that both groups of baroreceptors must be present to keep mean arterial pressure at its normal level. Moreover, both receptor groups are equally important in reducing APL. Ventilation contributes to generation of APL after total or selective baroreceptor removal. Such ventilation-induced pressure changes are kept at a minimum in baroreceptor-intact rats.
Mechanisms of cardiovascular responses to glycine injected into the dorsal vagal motor nucleus in rat.
Authors: Talman W T , Robertson S C , Cassell M D
Published: August 2012

Microinjection of glycine into the dorsal vagal motor nucleus of anesthetized rats elicits increases in arterial pressure and heart rate. In the nucleus tractus solitarii, where cardiovascular responses to injection of glycine may be mediated through release of acetylcholine, there is a dense concentration of glycinergic nerve terminals and glycine receptors. In this study, using immunohistochemical methods, we show that glycine terminals and receptors are present in caudal dorsal vagal motor nucleus, although the concentration of both terminal elements is less than in adjacent nucleus tractus solitarii. Responses to glycine microinjected into the dorsal vagal motor nucleus are blocked by the muscarinic antagonist atropine microinjected at the same site; but, unlike responses to glycine in the nucleus tractus solitarii, responses to glycine in the dorsal vagal motor nucleus are not prolonged by physostigmine. These data support the possibility that endogenous glycine may play a role as a transmitter in the dorsal vagal motor nucleus. Responses to glycine may be mediated through actions at muscarinic receptors but not through acetylcholine itself.
Vascular reactivity in young adults and cardiovascular disease. A prospective study.
Authors: Coresh J , Klag M J , Mead L A , Liang K Y , Whelton P K
Published: August 2012

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.
Endothelium-dependent and endothelium-independent effects of adenosine diphosphate in renovascular hypertension.
Authors: Almeida P J , Bissoli N S , Carvalhinho F B , Cabral A M
Published: August 2012

Norepinephrine-induced responses in isolated perfused mesenteric vascular bed from normotensive and renovascular hypertensive rats were examined in the presence of adenosine diphosphate (ADP, 2 x 10(-6) M). Responses to norepinephrine were significantly greater in vessels from hypertensive rats. Norepinephrine-induced contractions increased after the removal of endothelium. N omega-Nitro-L-arginine (L-NOARG), a potent inhibitor of nitric oxide formation, similarly increased contractions. The greatest responses were obtained, however, after treatment of the vascular segments with methylene blue. The presence of ADP caused significant endothelium-dependent decreases in contractions. Although decreases caused by ADP in vessels with endothelium after treatment with L-NOARG were not statistically significant, a tendency to decreased responses seems to suggest that L-NOARG diminishes but does not completely prevent the effect of ADP in mesenteric vessels. Methylene blue partially reduced the endothelium-dependent ADP-induced relaxant effects in sham-operated nephrectomized rats. A tendency to increased contractions to norepinephrine was observed in the presence of ADP after removal of endothelium. Thus, in the mesenteric resistance arteries of the rat under stimulation by ADP, it appears that nitric oxide released from L-arginine and the activity of soluble guanylate cyclase account only in part for the endothelium-dependent decreased responses to norepinephrine. When nitric oxide formation or soluble guanylate cyclase activity are depressed simultaneously with endothelium damage, ADP released from platelets or red blood cells may be an important factor that acts synergically with vasoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
Submandibular enzymatic vasoconstrictor messenger RNA in rat kidney.
Authors: Saed G M , Beierwaltes W H , Carretero O A , Scicli A G
Published: August 2012

Recently, we reported the isolation and identification of a potent vasoconstrictor enzyme from the rat submandibular gland, a member of the rat kallikrein gene family, which we named submandibular enzymatic vasoconstrictor (SEV). We studied whether messenger RNA (mRNA) for SEV is present in the kidney and isolated glomeruli, using the polymerase chain reaction assay with primers specific to the entire rat kallikrein family that would amplify a 430-bp fragment from their mRNA. As a probe we used a phosphorus-32-labeled oligonucleotide specific for SEV mRNA. A fragment of the predicted size was obtained on Southern blot for amplified renal RNA; however, no signal was obtained with glomerular RNA. To further confirm the presence of SEV mRNA in the kidney, polymerase chain reaction was repeated using primers specific to SEV mRNA that would amplify a 372-bp fragment from SEV mRNA alone. Again, a fragment of the predicted size was obtained on Southern blot after amplification of renal RNA but not RNA from the glomeruli. Southern blot of polymerase chain reaction-amplified RNA with primers that amplified the entire kallikrein gene family, using kallikrein complementary DNA that recognizes all members of the kallikrein gene family as a probe, revealed a 430-bp fragment for both renal and glomerular RNA, indicating that glomeruli contain mRNA for a member or members of the kallikrein family other than SEV. When the Southern blots were hybridized with a 32P-labeled oligonucleotide probe specific for glandular kallikrein, a fragment of the predicted size was obtained from amplified renal RNA but not glomerular RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Facilitation of noradrenergic transmission by angiotensin in hypertensive rats.
Authors: Faria F A , Salgado M C
Published: August 2012

We examined the angiotensin-induced potentiation of noradrenergic transmission in the isolated mesenteric arteries of one-kidney, one clip (1K1C) hypertensive rats. The angiotensin converting enzyme activity measured in plasma did not change during the development of hypertension, whereas the activity measured in the aortic tissue was significantly augmented 28 days after the renal artery was clipped. Although the pressor responses to nerve stimulation were basically unaltered, a significant increase in the sensitivity to norepinephrine developed during hypertension. The 1K1C preparations presented an increased sensitivity to the facilitatory effect of angiotensin II on the response to periarterial nerve stimulation. The facilitatory effect of angiotensin II on both nerve stimulation and exogenous norepinephrine was blocked by saralasin. Angiotensin I induced similar facilitatory action on noradrenergic transmission that was inhibited by saralasin. When a high concentration of angiotensin I was used, the facilitatory effect was significantly higher in mesenteric arteries from 1K1C rats than in controls. Captopril reduced the facilitatory effect of angiotensin I in 1K1C preparations, whereas the responses of the normotensive control rats were unaffected by captopril. These findings are consistent with angiotensin I acting directly on angiotensin II receptors or with angiotensin I being converted to angiotensin II by an alternative pathway not involving angiotensin converting enzyme.
Renin distribution in the rabbit renal microvasculature.
Authors: Juncos L A , Ito S , Nobiling R , Carretero O A
Published: August 2012

Immunocytochemical studies have shown that renin, which is normally located in the juxtaglomerular afferent arteriole, may also be found farther upstream toward the interlobular artery during chronic stimulation of the renin-angiotensin system. We assessed the renin distribution along the renal microvasculature using both quantitative analysis and immunocytochemistry in rabbits that received a normal sodium diet (0.48% NaCl), a low sodium diet (0.04% NaCl), or enalapril (1 mg/kg/day) for 4 weeks. From the outer cortex we microdissected 1) the proximal portion of the afferent arteriole (p-AF) extending from the interlobular artery to a point 50 microns from the glomerulus, 2) the distal 50 microns including its intact terminus (d-AF), and 3) the glomerulus without the vascular pole (GL) and measured their renin content. In controls, renin was 0.3 +/- 0.2, 27.0 +/- 5.2, and 2.8 +/- 0.5 ng angiotensin I/hr/arteriole (or GL) in the p-AF, d-AF, and GL, respectively. The low sodium diet and enalapril increased renin in the d-AF (53.1 +/- 6.9 and 68.4 +/- 8.1, respectively) but not in the GL (3.3 +/- 1.0 and 3.6 +/- 0.7). In the p-AF, both caused a small increase (delta = 1.5); however, this increase was minuscule compared with the large increase in the d-AF (delta = 41).(ABSTRACT TRUNCATED AT 250 WORDS)
Nonprostanoid endothelium-derived factors inhibit renin release.
Authors: Beierwaltes W H , Carretero O A
Published: August 2012

Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Renin-angiotensin-aldosterone system in normal and hypertensive pregnancy. Response to postural stimuli.
Authors: Fagundes V G , Lamas C C , Francischetti E A
Published: August 2012

Most studies that have attempted to distinguish pregnancy-induced hypertension from chronic hypertension in pregnancy include arbitrary clinical definitions and morphological reports based on renal biopsy. To evaluate whether these conditions have different responses to stimuli to the renin-angiotensin-aldosterone system, we studied four normal nonpregnant women, eight normal pregnant women, 10 women with pregnancy-induced hypertension, and 14 with chronic hypertension in pregnancy, in the third trimester of pregnancy, after they had sequentially adopted the supine, the left lateral recumbent, and the orthostatic positions for 90 minutes each. Postural maneuvers did not significantly change mean arterial pressure in pregnancy-induced hypertensive or in normal pregnant women, although in chronic hypertensive women, a significant reduction in this parameter was observed in left lateral recumbency. The renin-angiotensin-aldosterone system was significantly less activated with women in the supine position in pregnancy-induced hypertensive and chronic hypertensive women; however, as opposed to pregnancy-induced hypertensive women, those with chronic hypertension reassumed their humoral response to upright posture, which was accompanied by a significant reduction in sodium excretion. The parallelism between plasma renin activity and aldosterone levels, absent in normal pregnancy, returned in pregnancy-induced hypertensive and chronic hypertensive women in the erect posture (r = 0.73, p less than 0.01; r = 0.68, p less than 0.01, respectively). These data suggest that the adoption of the left lateral recumbent position in pregnancy reduces mean arterial pressure only in chronic hypertensive women. Moreover, in chronic hypertension, the upright position provoked a significant response of the renin-angiotensin-aldosterone system. This effect was not observed in women with pregnancy-induced hypertension.
Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein.
Authors: Guimarães C L , Calixto J B , Rae G A
Published: August 2012

In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions. The apparent EC50 values and maximal responses to 30 nM endothelin were 1.4 nM and 0.96 g for endothelin-1, 5.2 nM and 0.65 g for endothelin-2, and 1.7 nM and 0.62 g for endothelin-3 (n = 4-12). At concentrations producing half the contraction triggered by 80 mM KCl, the order of potencies was endothelin-1 greater than U46619 = angiotensin II greater than bradykinin greater than substance P greater than phenylephrine. Longitudinal portal-mesenteric vein preparations developed very modest contractions to endothelin-1 (0.13 g at 30 nM; n = 5), but their responses to 80 mM KCl and phenylephrine were greater than those of rings. Responses of rings to endothelin-1 were profoundly reduced in Ca(2+)-free medium, but less inhibition was obtained after incubation with nicardipine (up to 1 microM) and/or nickel (up to 0.5 mM), phorbol (up to 0.3 microM), staurosporine (up to 10 nM), or cromakalim (3 microM). Indomethacin (5.6 microM) did not affect responses to endothelin-1. Cromakalim (0.1-3 microM) also relaxed rings constricted with 0.3 nM endothelin-1, and this effect was partially reversed by glibenclamide (3 microM). Thus, endothelins, especially endothelin-1, are potent constrictors of portal vein rings but not of portal-mesenteric vein strips. Their action appears to rely largely on Ca2+ influx from the external medium (only in part via L- and T-type Ca2+ channels) and activation of protein kinase C but not on eicosanoid generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats.
Authors: Nguyen P V , Parent A , Deng L Y , Flückiger J P , Thibault G , Schiffrin E L
Published: August 2012

The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2 +/- 0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106 +/- 22 fmol/mg protein) than in uninephrectomized rats (172 +/- 19 fmol/mg protein, p less than 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with [3H]myoinositol. Inositol phosphates were separated by high-performance liquid chromatography. In response to 100 nmol/l ET-1, accumulation of inositol 1,4,5-trisphosphate after 20 seconds and of inositol monophosphate, inositol bisphosphate, and inositol 1,3,4-triphosphate after 30 minutes (in the presence of 25 mmol/l LiCl) were significantly lower in DOCA-salt hypertensive than in uninephrectomized control rats, in both aorta and mesenteric arteries. In conclusion, decreased density of ET-1 receptors in DOCA-salt hypertensive rats results in decreased activation of phospholipase C and, consequently, reduced vasoconstriction induced by ET-1. Because the decrease in vasoconstrictor effects of ET-1 is found in the absence of endothelium, it is likely that receptor downregulation rather than prior receptor occupancy underlies these findings.