bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of nifedipine on renal function in patients with essential hypertension.
Authors: Reams G P , Hamory A , Lau A , Bauer J H
Published: June 2012

Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist nifedipine (30-120 mg/day given in divided doses) administered for 4 weeks. Nifedipine monotherapy effectively lowered blood pressure in 73% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 13.3 and 19.6%, respectively. The filtration fraction and urinary albumin excretion remained unchanged. Renal vascular resistance was markedly reduced (25.2%). Changes observed in renal function were independent of the patients' initial glomerular filtration rate. Furthermore, there was no correlation between the systemic and renal effects of nifedipine monotherapy. Patients with a poor systemic blood pressure response exhibited increases in both glomerular filtration rate (+13%) and effective renal plasma flow (+20%), changes comparable with increases in glomerular filtration rate (+13%) and effective renal plasma flow (+19%) observed in patients achieving a goal blood pressure response (diastolic blood pressure less than or equal to 90 mm Hg, or a greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or both). These results suggest that nifedipine monotherapy has the potential to improve renal function abnormalities encountered in the essential hypertensive state independently of its effect on systemic blood pressure.
Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.
Authors: Minuz P , Covi G , Paluani F , Degan M , Lechi C , Corsato M , Lechi A
Published: June 2012

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2 were measured, along with renal prostaglandin E2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin F1 alpha, and 2,3-dinor-6-keto-prostaglandin F1 alpha were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2 and 2,3-dinor-thromboxane B2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p less than 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1 alpha and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.
Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats.
Authors: Lüscher T F , Diederich D , Weber E , Vanhoutte P M , Bühler F R
Published: June 2012

Endothelium-dependent relaxations are impaired in the aorta of various models of hypertension, but no data are available regarding the cerebral or renal circulation. Endothelium-dependent relaxations were studied in the carotid and renal artery of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Rings with and without endothelium were suspended in organ chambers for isometric tension recording. Acetylcholine and adenosine 5'-diphosphate (ADP) caused endothelium-dependent relaxations in both arteries that were impaired in the carotid, but not in the renal artery, of the SHR, similar to those to the endothelium-independent vasodilator sodium nitroprusside. Indomethacin did not affect relaxations to acetylcholine in the carotid artery, but it significantly augmented them in the renal artery. This finding suggests that an impaired vascular responsiveness to endothelium-derived relaxing factor is responsible for the decreased relaxations in the carotid artery of the SHR. In the renal artery, acetylcholine appears to release both endothelium-derived relaxing factor and a vasoconstrictor prostanoid. Carotid arteries of SHR were more sensitive to the constrictor effects of serotonin than were those of WKY. Endothelium removal caused a twofold to eightfold increase in sensitivity to serotonin in both strains. Thus, endothelium-dependent relaxations to acetylcholine and ADP are reduced and constrictions to serotonin are enhanced in the carotid, but not in the renal, artery of the SHR.
Potentiation of sympathetic nerve responses to hypoxia in borderline hypertensive subjects.
Authors: Somers V K , Mark A L , Abboud F M
Published: June 2012

We tested the hypothesis that sympathetic nerve responses to stimulation of chemoreceptors by hypoxia are exaggerated in borderline hypertensive humans. We compared responses to isocapnic hypoxia in eight borderline hypertensive subjects and eight normotensive control subjects matched for age, sex, weight, and height without a family history of hypertension. Measurements of heart rate, mean blood pressure, minute ventilation, and sympathetic nerve activity to muscle were made before and during hypoxia. We also measured responses to a period of voluntary apnea during hypoxia. There were no significant differences between the increases in heart rate, blood pressure, and ventilation in response to hypoxia in the two groups. However, during hypoxia sympathetic activity in the hypertensive subjects increased by 40.6 +/- 13.6% (mean +/- SE), greater than the increase of 20.4 +/- 5.0% in the control subjects (p less than 0.05). In six hypertensive and six control subjects, when apnea was performed during hypoxia, sympathetic activity increased by 605.0 +/- 294.3% in the hypertensive subjects and by only 52.8 +/- 17.3% in the control subjects (p less than 0.001). We conclude that the chemoreceptor reflex is enhanced in borderline hypertensive subjects and results in exaggerated increases in sympathetic nerve activity during hypoxia. This enhanced chemoreceptor reflex is especially obvious when the inhibitory influence of breathing and thoracic afferent activity is eliminated by apnea. This exaggerated response may contribute to excess sympathetic activity in borderline hypertensive subjects and to adverse consequences of sleep apnea in hypertensive subjects.
Altered biochemical and functional responses in aorta from hypertensive rats.
Authors: Jones A W , Geisbuhler B B , Shukla S D , Smith J M
Published: June 2012

Factors that lead to supersensitivity of vascular smooth muscle to norepinephrine during aldosterone-salt-induced hypertension in rats appear to reside beyond ligand-alpha-adrenergic receptor binding, which we have shown previously to be normal. The objective of this study was to determine whether significant shifts occur in the coupling between receptors and the production of putative second messengers. Measures of [3H]myo-inositol phosphates in aorta (endothelium removed) exhibited a concentration-dependent increase to norepinephrine, with the 50% response shifted significantly to the left in the hypertensive group (7.0 +/- 0.9 X 10(-7) M in 8 control rats vs 1.1 +/- 0.2 X 10(-7) M in 8 hypertensive rats; p less than 0.001). The production of [32P]phosphatidic acid was also shifted (6.5 +/- 2.5 X 10(-7) M in 16 control vs 1.9 +/- 0.8 X 10(-7) M in 12 hypertensive rats; p less than 0.05). The functional responses of 42K efflux and contraction to norepinephrine were also significantly shifted threefold to 15-fold in the hypertensive group (p less than 0.001), but the 50% response typically occurred at a 10 to 100 times lower concentration than that for the production of myo-inositol phosphates and phosphatidic acid. The amplification between receptor occupancy and functional responses apparently occurs beyond the production of phosphoinositide metabolites. The fivefold shift in the 50% response of biochemical end points for the hypertensive group accounted for most of the shift (sixfold) in the functional end points.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased alpha-adrenergic receptor affinity in resistance vessels from hypertensive rats.
Authors: Nyborg N C , Bevan J A
Published: June 2012

alpha-Adrenergic receptor-related properties, specifically, norepinephrine affinity, occupancy and reserve during contraction, were determined in segments of rat resistance arteries. These were obtained from the superior mesenteric bed of spontaneously hypertensive rats and Wistar-Kyoto strain controls. Receptor affinity for norepinephrine in the spontaneously hypertensive rats was significantly greater than that for the Wistar-Kyoto controls. There were no differences in the estimates of receptor occupancy and reserve. This finding taken together with other studies is consistent with the conclusion that increased alpha-adrenergic receptor-mediated sensitivity of vascular smooth muscle of the spontaneously hypertensive rat reflects differences in the agonist site on the alpha-adrenergic receptor.
The effects of urinary digitalislike factor on cultured vascular smooth muscle cells.
Authors: Goto A , Yamada K , Ishii M , Yoshioka M , Ishiguro T , Sugimoto T
Published: June 2012

We attempted to purify a digitalislike factor from human urine. On the assumption that a natural ligand for the digitalis receptor should be searched for on the basis of the effects on intact cells, we used an inhibitory effect on the binding of [3H]ouabain to human erythrocytes to determine digitalislike activity. A highly polar [3H]ouabain displacing activity was obtained by a combination of chromatographic procedures including reverse-phase high performance liquid chromatography. Urine-derived [3H]ouabain displacing activity, a competitive inhibitor of ouabain binding to human erythrocytes, acted on human lymphocytes in a similar manner. The dose-response curve of this compound was parallel to that of ouabain. Urine-derived [3H]ouabain displacing activity significantly inhibited monensin-stimulated increase in ouabain-sensitive 86Rb uptake, a parameter of Na+,K+-adenosine triphosphatase (ATPase), by 95% (p less than 0.01) in cultured vascular smooth muscle cells (A10 cells). Furthermore, this compound enhanced net 45Ca influx by 30% (p less than 0.01) and reduced 45Ca efflux by 35% (p less than 0.01) in A10 cells. These results suggest that urine-derived [3H]ouabain displacing activity may be a regulator of Na+,K+-ATPase and a modulator of vascular tone.
Endogenous intrarenal adenosine preserves renal blood flow in one-kidney, one clip rats.
Authors: Katholi R E , Creek R D , McCann W P
Published: June 2012

Intrarenal adenosine concentration is threefold greater in the one-kidney, one clip hypertensive rat compared with normotensive animals. Since exogenously administered adenosine may increase renal blood flow by direct vasodilation, inhibition of renin release, or prejunctional interruption of adrenergic neurotransmission, these studies examined whether endogenous intrarenal adenosine maintains renal blood flow distal to renal arterial stenosis. Administration of theophylline, which blocks the direct vasodilating effect of adenosine and antagonizes the inhibitory effect of adenosine on renin release and sympathetic neurotransmission, resulted in marked renal vasoconstriction in one-kidney, one clip hypertensive animals. This theophylline-induced renal vasoconstriction was markedly attenuated by angiotensin II blockade with saralasin and was unchanged by renal denervation or beta 1-adrenergic blockade with atenolol. These findings indicate that the marked renal vasoconstriction in one-kidney, one clip hypertension during theophylline administration is mainly mediated by angiotensin II, is to a lesser degree due to inhibition of adenosine-induced vasodilation, and is independent of sympathetic influences. These data suggest that endogenous interstitial adenosine preserves renal blood flow in one-kidney, one clip hypertension mainly by inhibiting renin release.
Renal cortical and papillary blood flow in spontaneously hypertensive rats.
Authors: Roman R J , Kaldunski M L
Published: June 2012

The present study examined whether an alteration in renal medullary hemodynamics is associated with the development of hypertension in the spontaneously hypertensive rat (SHR). The relationships between whole kidney, cortical and papillary blood flows, and renal perfusion pressure were compared in 3- to 5-, 6- to 9-, and 12- to 16-week-old SHR and Wistar-Kyoto rats (WKY). Cortical and papillary blood flows were similar in the different age groups of SHR and WKY over most of the range of perfusion pressure studied. Control papillary blood flows, determined at a renal perfusion pressure equal to the mean arterial pressure of each animal, were not significantly different in the 3- to 5- and 12- to 16-week-old SHR in comparison to values observed in age-matched WKY. In contrast, the control papillary blood flow was 30% lower in 6- to 9-week-old SHR in comparison to the value observed in WKY. Papillary blood flows were significantly less in all age groups of SHR than the corresponding flows measured in WKY when they were compared at equivalent renal perfusion pressures. These findings indicate that medullary vascular resistance is elevated even in very young SHR and suggest that alterations in vasa recta hemodynamics may participate in the development of hypertension by shifting the pressure-natriuresis relationship toward higher pressures.
Glycine microinjected in the rat dorsal vagal nucleus increases arterial pressure.
Authors: Talman W T
Published: June 2012

Microinjections (25 nl) of glycine into the dorsal motor nucleus of the vagus in 21 rats elicited dose-dependent increases of arterial pressure and heart rate that were not seen with injections adjacent to the dorsal motor nucleus of the vagus. The responses to glycine were neurally mediated and could be blocked either by local pretreatment with strychnine or by combined vagotomy and ganglionic blockade. The data suggest that glycine receptors on, or in the region of, neurons of the dorsal motor nucleus of the vagus may have a role in the regulation of arterial pressure and heart rate.
Area postrema ablation and vascular reactivity in deoxycorticosterone-salt-treated rats.
Authors: Bruner C A , Mangiapane M L , Fink G D , Webb R C
Published: June 2012

In rats, central administration of the neurotoxin 6-hydroxydopamine prevents hypertension and certain functional vascular changes after deoxycorticosterone (DOC)-salt treatment. In this study, the effect of electrolytic ablation of the area postrema on blood pressure and vascular reactivity in DOC-salt-treated rats was examined. Four treatment groups of rats were studied (n = 5 in each): area postrema lesion, DOC-salt (DOC pivalate, 5 mg/wk s.c. for 5 weeks); sham lesion, DOC-salt; area postrema lesion, control; and sham lesion, control. Helically cut strips of carotid artery, aorta, and mesenteric artery were prepared for isometric force recording. Area postrema lesion attenuated hypertension in DOC-salt rats (mean arterial pressure, 107 vs 123 mm Hg in area postrema lesion and sham lesion rats, respectively; chronic aortic catheter). Vascular strips from sham lesion-control rats. These changes in vascular reactivity also were observed in area postrema lesion-DOC-salt rats. DOC treatment in rats on a normal sodium intake did not result in hypertension or increased vascular reactivity. In summary, integrity of the area postrema is necessary for hypertension but not for changes in vascular reactivity, in DOC-salt rats. It appears that 1) changes in vascular reactivity may be necessary, but they are not sufficient to produce DOC-salt hypertension, and 2) if these vascular changes are secondary to a central nervous system effect, they are mediated by a pathway distinct from the area postrema.
Contrasting reflex effects of chemosensitive and mechanosensitive vagal afferents.
Authors: Higuchi S , Morgan D A , Mark A L
Published: June 2012

Previous studies have identified two distinct types of cardiac vagal afferents, mechanosensitive and chemosensitive. We tested the hypothesis that these two types of vagal afferents mediate different reflex sympathetic nerve responses. We compared effects of stimulation of chemosensitive and mechanosensitive vagal afferents on renal and adrenal sympathetic nerve activity in rats. In anesthetized, sinoaortic baroreceptor-denervated rats, we measured arterial pressure, heart rate, and renal and adrenal sympathetic nerve activity during intrapericardial administration of phenyl diguanide as a stimulus for chemosensitive afferents and during volume expansion and acute occlusion of the ascending aorta as stimuli for mechanosensitive afferents. Stimulation of chemosensitive afferents with phenyl diguanide (3, 10, and 30 micrograms/kg intrapericardially) caused decreases in renal sympathetic nerve activity (-36 +/- 5, -52 +/- 11, and -71 +/- 5%; p less than 0.01) and in arterial pressure and heart rate but increased adrenal sympathetic nerve activity (+14 +/- 27, +63 +/- 21, and +83 +/- 28%; p less than 0.05). These responses were abolished by vagotomy. Intrapericardial injection of saline vehicle did not change renal and adrenal sympathetic nerve activity. In contrast to the effects of phenyl diguanide, activation of mechanosensitive afferents by volume expansion with intravenous infusion of 6% dextran in 0.9% saline (Dextran 75) decreased both renal and adrenal sympathetic nerve activity. Stimulation of mechanosensitive afferents by acute occlusion of the ascending aorta also decreased both renal and adrenal sympathetic nerve activity. These results indicate that chemosensitive and mechanosensitive cardiac vagal afferents produce different reflex responses: Chemosensitive afferents increase and mechanosensitive afferents decrease adrenal sympathetic outflow.
Neuronal responses to angiotensin II in the in vitro slice from the canine medulla.
Authors: Barnes K L , Knowles W D , Ferrario C M
Published: June 2012

The present studies utilized the in vitro slice preparation of the canine dorsomedial medulla, which we have recently developed, to obtain direct evidence for the effects of angiotensin II (Ang II) on the activity of single neurons in this region. Horizontally oriented slices (300 micron) containing the area postrema, nucleus tractus solitarii (NTS), and dorsal motor nucleus of the vagus were perifused with oxygenated artificial cerebrospinal fluid. The effects of microdrop application of Ang II and its antagonist [Sar1,Thr8]Ang II on spontaneous firing rate were determined in 27 extracellularly recorded neurons. Ang II substantially increased the firing rate of 13 neurons located in the medial NTS, but it did not alter the spontaneous activity of the remaining 14 neurons. In most cases Ang II elicited a slowly developing, prolonged excitatory response. The effects of both Ang II and [Sar1,Thr8]Ang II were tested in 13 neurons. [Sar1,Thr8]Ang II produced a short latency, brief excitation in three neurons, marked inhibition of spontaneous firing in two cells, and no effect on the other eight neurons. Administration of [Sar1,Thr8]Ang II blocked the excitatory effects of subsequent administration of Ang II in three neurons. To our knowledge, these observations provide the first evidence for direct actions of both Ang II and [Sar1,Thr8]Ang II on neurons in the canine NTS and for the specificity of the neuronal effects of Ang II as documented by blockade of the excitatory response to Ang II by [Sar1,Thr8]Ang II.
Autoregulation of the systemic circulation in conscious rats.
Authors: Hinojosa-Laborde C , Greene A S , Cowley A W
Published: June 2012

Autoregulation of blood flow in various organ systems is a well-documented phenomenon. However, the net effect of these regional autoregulatory responses on the systemic circulation has not been studied in conscious rats despite the now extensive use of rats in cardiovascular research. The ability of the systemic circulation to autoregulate cardiac output has been proposed to play an important role in the development of increased vascular resistance in volume-dependent forms of hypertension. To better understand these events, we characterized responses to acute increases and decreases in blood volume in conscious areflexic rats that were chronically instrumented with arterial and venous catheters and an electromagnetic flow probe around the ascending aorta. Neurohumoral blockade was achieved with chlorisondamine (10 mg/kg), methscopolamine (0.5 mg/kg), captopril (1.0 mg/kg), and d(CH2)5Tyr(Me)arginine vasopressin (10 micrograms/kg). Mean arterial pressure was restored to normal levels with a constant i.v. norepinephrine infusion, which resulted in normal values of cardiac output, total peripheral resistance, and blood gases. Blood volume expansion (0.9 ml i.v. blood infusion for 6 minutes) increased cardiac output 9 +/- 1% and mean arterial pressure 30 +/- 3% and caused a 22 +/- 2% increase in total peripheral resistance (n = 7). Blood volume contraction (6-minute withdrawal of 0.9 ml of blood) decreased cardiac output 12 +/- 1% and mean arterial pressure 26 +/- 4%, which resulted in a 16 +/- 4% decrease in total peripheral resistance (n = 8). The slopes of the pressure-flow relationships during volume expansion were 0.24 and 0.41 during volume contraction, as compared with a nonautoregulating system (slope = 1) and a completely autoregulating system (slope = 0).(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms underlying pressure-related natriuresis: the role of the renin-angiotensin and prostaglandin systems. State of the art lecture.
Authors: Romero J C , Knox F G
Published: June 2012

It has long been known that increments in renal perfusion pressure can induce an elevation of urine sodium excretion without changing renal blood flow or glomerular filtration rate. The mechanism underlying this pressure-related natriuresis remains undefined, although the interest in its elucidation has been stimulated by the notion that it may constitute the central phenomenon through which the kidney regulates blood volume and, thereby, blood pressure. Recently, the use of novel experimental techniques has disclosed some important clues about changes in renal hemodynamics that, along with changes in renal humoral regulators, allow us to visualize a possible sequence of events responsible for pressure-related natriuresis. According to this hypothesis, the autoregulatory responses responsible for maintaining glomerular filtration rate are elicited in preglomerular vasculature by changes in renal perfusion pressure. These myogenic responses are coupled through Ca2+ entry in juxtaglomerular cells with inversely related changes in the release of renin and, consequently, with the amount of angiotensin II generated in renal interstitium. The release of renin from juxtaglomerular cells is modulated by the synthesis of prostaglandin I2 from the adjacent endothelial cells. Interstitial angiotensin II could influence sodium tubular reabsorption directly by stimulating sodium transport in proximal renal tubules and indirectly by altering medullary blood flow and, thereby, medullary interstitial pressure. In the renal medulla, the effects of interstitial pressure on sodium reabsorption can be amplified by the release of prostaglandin E2 from interstitial cells. A deficient regulation of this relationship could result in a shift of the pressure-natriuresis curve, leading to hypertension.
Impaired release of atrial natriuretic factor in NaCl-loaded spontaneously hypertensive rats.
Authors: Jin H K , Chen Y F , Yang R H , Meng Q C , Oparil S
Published: June 2012

Our previous studies demonstrated that NaCl-sensitive spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit increased blood pressure and reduced noradrenergic input to the anterior hypothalamus area when fed high NaCl diets. The current study tested the hypotheses that 1) release of atrial natriuretic factor (ANF) into the plasma is impaired in NaCl-loaded SHR, a defect that would tend to elevate blood pressure, and 2) ANF levels in regions of brain involved in blood pressure regulation, such as the anterior hypothalamic area, are altered in SHR. SHR and control Wistar-Kyoto rats (WKY) were placed on 1% or 8% NaCl diets at age 7 weeks; 2 weeks later, ANF levels were measured in plasma, left and right atria, anterior hypothalamic area, ventral hypothalamic area, posterior hypothalamic area, pons, and medulla by radioimmunoassay. Blood for ANF assay was obtained from intra-arterial cannulas in conscious, unrestrained rats studied in the resting state. The 8% NaCl diet produced an increase in blood pressure in the SHR, but not in the WKY. Plasma ANF levels were significantly greater in WKY fed 8% NaCl than in WKY fed 1% NaCl, but dietary NaCl loading did not produce similar increases in plasma ANF in the SHR. Plasma ANF levels were not significantly different between SHR and WKY fed the 1% NaCl diet. The observation that dietary NaCl loading stimulated ANF release into the plasma in WKY but not in SHR suggests that the exacerbation in hypertension seen in NaCl-loaded SHR may be related to an impairment in ANF release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertensive dog plasma inhibits the Na+-K+ pump of cultured vascular smooth muscle.
Authors: Overbeck H W , Wallick E T , Shikuma R , Magargal W W
Published: June 2012

We investigated the effects of plasma from dogs with perinephritic hypertension on the Na+-K+ pump of cultured dog vascular smooth muscle cells. We also measured [3H]ouabain binding by myocardium and vascular tissue. Fresh, unprocessed plasma from healthy dogs during the first 6 weeks of benign one-kidney, one wrapped hypertension and from paired normotensive control dogs was layered over confluent primary cultured puppy aortic smooth muscle cells that had been sodium-loaded with monensin. In 26 paired assays of plasma from four pairs of dogs, cells incubated in the presence of plasma from hypertensive dogs had significantly reduced total (p less than 0.01) and ouabain-sensitive (p less than 0.001) 86Rb+ uptakes, but their intracellular sodium content did not differ from cells incubated in paired normotensive plasma. We no longer detected these uptake differences when passaged cells or cells cocultured with bovine endothelial cells were used for assay or when plasma was treated with protease inhibitors or boiled. However, boiled plasma increased the sodium content of the assay cells, suggesting an ionophorelike effect. Levels of pump inhibitory activity in plasma appeared to remain constant during Weeks 1 to 6 of hypertension. We found no evidence for altered numbers of pump sites in cardiovascular tissues from these hypertensive dogs. These findings support the hypothesis that plasma factors inhibit the membrane Na+-K+ pump in vascular smooth muscle cells in this form of hypertension. These plasma inhibitory factors apparently do not induce pump molecules.
Release of fatty acids by perfused vascular tissue in normotensive and hypertensive rats.
Authors: Mtabaji J P , Manku M S , Horrobin D F
Published: June 2012

The release of fatty acids from perfused mesenteries of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was studied. The release of the prostaglandin precursors dihomogammalinolenic acid, arachidonic acid, and eicosapentaenoic acid was reduced in SHR when compared with age-matched WKY. The release of all other fatty acids detected in the effluent was also reduced. The differences in fatty acid release were evident even when tissue levels of the fatty acids were similar or higher in SHR than in controls. The addition of evening primrose oil and fish oil into the diet partially corrected these defects. Evening primrose oil and fish oil both attenuated increases in blood pressure, but fish oil was more potent than primrose oil. Although both diets reduced vascular reactivity, primrose oil was more effective with lower doses of norepinephrine whereas fish oil blunted the effects of both low and high doses of norepinephrine. The possible mechanisms for the effects of primrose oil and fish oil on vascular reactivity are briefly discussed.
Vasoconstriction and hypersensitivity to vasoactive substances after acute volume expansion in dogs.
Authors: Otsuka A , Ogihara T , Kohara K , Mikami H , Katahira K , Tsunetoshi T , Kumahara Y
Published: June 2012

In a search for factors contributing to the sustained blood pressure (BP) elevation in acutely volume-loaded animals, dextran dissolved in lactated Ringer's solution (20 ml/kg) was infused into 34 mongrel dogs over a period of 1 hour under pentobarbital anesthesia and changes in hemodynamic and humoral variables were monitored during its infusion and for 3 hours after its infusion. BP elevation during volume loading (from 114 +/- 3 to 128 +/- 3 [SEM] mm Hg) was attributed to an increase in cardiac output. After volume loading, some dogs maintained BP elevation whereas others did not. The former group showed an increase in total peripheral resistance, demonstrating a transformation of cardiac output to total peripheral resistance as a responsible factor in maintenance of the elevated BP. The plasma levels of norepinephrine, vasopressin, and plasma renin activity were not elevated, indicating that these vasoactive factors were not responsible for elevation of the BP or total peripheral resistance. The changes in the hematocrit, atrial natriuretic factor, urine volume, and urinary sodium excretion were identical in the two groups, and natriuresis was not prominent when total peripheral resistance was high. Pressor responses to norepinephrine and angiotensin II were potentiated 3 hours after stopping infusion in both groups, but this potentiation was not correlated with the increase in total peripheral resistance or mean BP. Thus, acute volume expansion produced resistance-dependent hypertension following the initial volume-dependent hypertension. It is unlikely that a vascular sensitizing natriuretic factor plays a role in the resistance-dependent BP elevation. The mechanism and physiological importance of hypersensitivity to vasoactive substances remain to be elucidated.
Long-term microvascular response to hydralazine in spontaneously hypertensive rats.
Authors: Hutchins P M , Marshburn T H , Maultsby S J , Lynch C D , Smith T L , Dusseau J W
Published: June 2012

Chronic microcirculatory alterations produced by prolonged use of a vasoactive drug were repeatedly observed in the same skeletal muscle vessels of the dorsal microcirculatory chamber. Arterioles and venules with diameters averaging from 70 to 90 microns, the size range contributing most to peripheral vascular resistance, were measured daily for 6 days to determine differences in diameter, tortuosity, and number of branches. Hydralazine was given as a subcutaneous pellet (2.5 mg), with a release life of 21 days. Hydralazine caused a 39% dilation in arterioles of Wistar-Kyoto rats (WKY) at 3 hours but only an 8% dilation in those of spontaneously hypertensive rats (SHR). At 6 hours, arterioles in both groups were similarly dilated (30-33%). Beyond 6 hours, both SHR and WKY arterioles returned to their prehydralazine control diameter, even though arterial pressure was still reduced. By Day 6, in WKY, but not SHR, there was an increase in the tortuosity of arterioles and a tendency for an increase in their number. Venous diameter was also increased on Day 6, consistent with the fluid retention effect of hydralazine. These data indicate that some so-called vasodilators may cause long-term alterations in growth of vessels rather than an increase in vessel caliber.
Renal alpha 1-adrenergic receptor response coupling in spontaneously hypertensive rats.
Authors: Jeffries W B , Yang E , Pettinger W A
Published: June 2012

Renal sympathetic antidiuretic, antinatriuretic, and vasoconstrictor responses are mediated by alpha 1-adrenergic receptors in the normal rat. Since the renal nerve has been implicated in the pathogenesis of rat genetic hypertension, we investigated renal alpha 1-adrenergic receptor coupling to phosphoinositide turnover in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In cortical slices from adult (13-week-old) SHR and WKY, stimulation with norepinephrine (10(-7)-10(-3) M) caused a concentration-dependent increase in accumulation of [3H]inositol phosphates. However, dose-response curves for SHR characteristically displayed a depression of the maximum response as compared with those for WKY. Baseline accumulation of [3H]inositol phosphates was not different between strains (39.4 +/- 2.2 cpm/mg tissue/hr for WKY and 34.4 +/- 2.1 cpm/mg tissue/hr for SHR slices; n = 5 rats/group, determined in triplicate). Antagonist competition studies revealed that norepinephrine-stimulated (10(-4) M) [3H]inositol phosphate accumulation was mediated by alpha 1-adrenergic receptors (IC50) for prazosin: 65 +/- 11 nM for SHR and 64 +/- 5 nM for WKY). The reduction in norepinephrine-stimulated [3H]inositol phosphate accumulation in SHR cortex was not the result of the hypertension, since it was also present in cortical slices from young (4-week-old) SHR in which the blood pressure was not yet significantly different from that in WKY and since [3H]inositol phosphate accumulation was unchanged from control values in rats made hypertensive by treatment with deoxycorticosterone acetate. Scatchard analysis of [3H]prazosin binding in renal cortical membranes of young and adult SHR and WKY revealed no significant differences in alpha 1-adrenergic receptor density or affinity between strains at either age. Our results suggest that renal alpha 1-adrenergic receptor coupling to phospholipase C is less efficient in SHR than in WKY. This impaired response is not the result of hypertension or changes in receptor density; this defect may play a role in increased renal sympathetic nerve activity and in the development or maintenance of hypertension in SHR.
Diagnosis ex juvantibus. Individual response patterns to drugs reveal hypertension mechanisms and simplify treatment.
Authors: Laragh J H , Lamport B , Sealey J , Alderman M H
Published: June 2012

Heterogeneity of response to antihypertensive therapy is a well-recognized clinical phenomenon. An agent that is antihypertensive in one patient may increase blood pressure in another or have no effect in a third. We believe that this variety of individual response to drug treatment can provide a new framework for the study of hypertensive subjects. Different patterns of response elicited by sequential trials of individual drugs with different mechanisms of action (diuretics, calcium channel blockers, alpha-blockers, beta-blockers, and converting enzyme inhibitors) should provide another means to classify hypertensive patients into biologically relevant groups. The documentation and analysis of this therapeutic heterogeneity in relation to renin profiling and to other physiological and demographic parameters may add a new dimension to the investigation of the pathophysiology of hypertension; it may serve as a basis for more appropriate stratification of participants in clinical trials and may ultimately contribute to a more rational approach to patient management.
Effect of protein kinase C activation on cytoskeleton and cation transport in human erythrocytes. Reproduction of some membrane abnormalities revealed in essential hypertension.
Authors: Postnov Y V , Kravtsov G M , Orlov S N , Pokudin N I , Postnov I Y , Kotelevtsev Y V
Published: June 2012

Certain manifestations of alterations of membrane cytoskeleton, protein kinase C activity, and ion transport were revealed in erythrocytes of patients with essential hypertension: 1) the average volume of erythrocytes is reduced by 4%; 2) about 7% of the total number of erythrocytes is represented by cup-shaped forms compared with 1.5 to 3.0% in the control group; 3) basal phosphorylation of Band 4.9 protein is increased 1.6-fold to 1.8-fold; 4) activity of protein kinase C is increased by 60 to 70%; 5) the rate of proton electrochemical gradient (delta mu H+)-induced Na+-H+ exchange is increased twofold. Treatment of erythrocytes of healthy donors with protein kinase C activator (12-O-tetradecanoylphorbol-13-acetate) leads to similar but more marked changes in cell shape (17% of cup-shaped forms), volume reduction (by 7%), an increase of Band 4.9 protein phosphorylation (threefold), and an increase in the rate of Na+-H+ exchange (fourfold). Protein kinase activation does not modify Na+-Li+ exchange and slightly increases (by 20-50%) Na+-K+ pump activity, Na+-K+ cotransport, and the rate of 45Ca influx. It may be assumed that the increase of protein kinase C activity is one of the most probable molecular mechanisms conditioning abnormalities of the membrane skeleton and Na+-H+ exchange in primary hypertension.
Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.
Authors: Salazar F J , Bolterman R , Fiksen-Olsen M J , Quesada T , Romero J C
Published: June 2012

The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.
Arterial vascular compliance response to vasodilators by Fourier and pulse contour analysis.
Authors: Finkelstein S M , Collins V R , Cohn J N
Published: June 2012

Vasodilator drugs are widely used in the management of cardiovascular disease. They decrease systemic vascular resistance, but they also may influence vascular arterial compliance. This study evaluated the effects of three vasodilators--nitroprusside, nitroglycerin, and hydralazine--on vascular compliance using impedance parameters determined by pulse contour and Fourier analyses. The open chest study was performed on anesthetized dogs. Mean arterial pressure decreased by a minimum of 20% after vasodilator intervention. The decrease in systemic vascular resistance was significant (p less than 0.01) only after hydralazine treatment. Proximal compliance increased after administration of all drugs, but the increase was not statistically significant. Distal compliance determined by pulse contour analysis increased by 60 to 120% after all three drug treatments (p less than 0.05 for nitroprusside, p less than 0.02 for nitroglycerin and hydralazine). Characteristic impedance from Fourier analysis responded variably, and changes were not statistically significant. The sensitivity of changes in distal compliance as a marker for the vascular effect of these drugs suggests that it might be used as a more reliable guide than blood pressure or vascular resistance in monitoring clinical response to such intervention. The more traditional measure of characteristic impedance provides a vascular measurement that is less sensitive than distal compliance to the effects of these vasodilator drugs.
Free cytosolic calcium in renal proximal tubules from the spontaneously hypertensive rat.
Authors: Llibre J , LaPointe M S , Batlle D C
Published: June 2012

Free intracellular calcium was measured in renal proximal tubules obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto rats (WKY) ingesting a normal diet. Experiments were performed on renal proximal tubule suspensions using fura-2 to monitor cytosolic calcium. In 4-week-old rats, when systolic blood pressure was not significantly different between the two groups, renal proximal tubule cytosolic calcium was similar (143 +/- 28 and 144 +/- 15 nM, respectively). By the age of 5 weeks, cytosolic calcium increased significantly in both SHR and WKY (214 +/- 24 and 262 +/- 34 nM, respectively, p less than 0.05). Calcium, however, was not significantly different between the two groups, even though at this age blood pressure was higher in SHR than in WKY. As compared with values in 4-week-old rats, cytosolic calcium was also found increased in tubules from both SHR and WKY aged 10 to 12 weeks (261 +/- 42 and 279 +/- 30 nM, respectively) and 20 to 24 weeks (263 +/- 42 and 308 +/- 28 nM, respectively). However, no significant differences in cytosolic calcium were found between SHR and WKY even though at these ages systolic blood pressure increased markedly in the SHR. Moreover, regression analysis failed to reveal a correlation between cytosolic calcium and blood pressure when data from either group of rats of all ages studied were pooled. Exposure to ouabain (10(-3) M) to inhibit Na+,K+-adenosine triphosphatase and increase intracellular sodium had no significant effect on cytosolic calcium in tubules from either SHR or WKY (260 +/- 69 and 250 +/- 45 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of incremental infusions of atrial natriuretic factor on aldosterone, renin, and blood pressure in humans.
Authors: Oelkers W , Kleiner S , Bähr V
Published: June 2012

To evaluate the physiological effects of human atrial natriuretic factor-(99-126) (ANF), we infused ANF, 0.1, 0.3, and 1.0 micrograms/min, or placebo for 125 minutes on different days into six sodium-deprived normal men. During the last 45 minutes of infusion, angiotensin II, 6 ng/kg/min, was infused. Blood pressure, heart rate, plasma concentrations of ANF, aldosterone, and cortisol, and plasma renin activity (PRA) were measured before and during infusion. Steady state mean plasma ANF levels during infusion were 26.2 (placebo), 68.8 (0.1 micrograms ANF/min), 221 (0.3 micrograms ANF/min), and 648 pg/ml (1.0 microgram ANF/min). Systolic blood pressure fell significantly (with 1.0 microgram ANF/min), and diastolic pressure tended to rise in a dose-dependent manner, while heart rate was unchanged. PRA and plasma aldosterone fell during ANF infusion in a dose-dependent manner (significant with 0.3 and 1.0 microgram ANF/min infused). The blood pressure-raising and aldosterone-stimulating effects of angiotensin II were blunted by ANF (significant only with 1.0 microgram ANF/min). It is concluded that effects of ANF on blood pressure and the renin-aldosterone system occur with plasma ANF levels close to the physiological range, as well as with slightly elevated ANF levels, as observed in congestive heart failure and renal insufficiency.
Altered hemodynamics during exercise in older essential hypertensive subjects.
Authors: Montain S J , Jilka S M , Ehsani A A , Hagberg J M
Published: June 2012

This study was designed to compare the resting and exercise hemodynamics of older adults with moderate hypertension with those of age-matched normotensive controls. Thirty-one hypertensive (20 men, 11 women; mean age, 63.9 +/- 2.8 years) and 28 normotensive subjects (15 men, 13 women; mean age, 62.6 +/- 2.4 years) were studied. There were no differences between the groups in terms of body weight, body composition, and maximal O2 consumption (VO2). At rest, there were no differences in VO2, cardiac output, stroke volume, or heart rate between the two groups, although systolic (158 +/- 13 vs 121 +/- 12 mm Hg) and diastolic blood pressures (94 +/- 7 vs 79 +/- 8 mm Hg) were higher in the hypertensive subjects. The hypertensive subjects' elevated blood pressure at rest was the result of a higher total peripheral resistance. During exercise, the hypertensive subjects had a lower cardiac output and stroke volume, no difference in heart rate and VO2, higher systolic, diastolic, and mean blood pressures, and a higher total peripheral resistance compared with their normotensive peers. The results indicate that older hypertensive persons have an altered cardiovascular response to exercise as compared with age-matched normotensive subjects. The responses also indicate that older essential hypertensive persons do not undergo excessive myocardial demands during exercise of the intensity usually prescribed in rehabilitation programs.
Initial antihypertensive drug therapy. Final report of a randomized, controlled trial comparing alpha-blocker and diuretic.
Authors: Stamler R , Stamler J , Gosch F C , Berkson D M , Dyer A R , Hershinow P
Published: June 2012

We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
The international standard for atrial natriuretic factor. Calibration by an international collaborative study.
Authors: Poole S , Gaines Das R E , Dzau V J , Richards A M , Robertson J I
Published: June 2012

An ampouled preparation of human atrial natriuretic factor, ANF-(99-126), was evaluated by 23 laboratories in 10 countries for its suitability to serve as the international standard for ANF. The preparation was calibrated by radioimmunoassay, radioreceptor binding assay, and bioassay and was shown to have satisfactory stability and biological activity. Estimates of the ANF content of a set of specimens of plasma in terms of the standard showed agreement in ranking order when the ANF was extracted prior to assay. However, estimates of the ANF content of the plasmas in terms of either the international standard or the various local standards varied widely among laboratories. On the basis of the results reported here, with the agreement of the participants in the study and with the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 85/669 was established in 1987 as the international standard for ANF, with a defined potency of 2.5 international units per ampoule.