bluuebunny/crossref_metadata_2025 huggingface dataset:
A kallikrein-like enzyme in the aorta of normotensive and hypertensive rats.
Authors: Madeddu P , Varoni M V , Demontis M P , Fattaccio M C , Parpaglia P P , Glorioso N
Published: June 2012

We evaluated whether vascular kallikrein is altered in rats with genetic or experimental hypertension. Group 1 was infused intraperitoneally with angiotensin II (Ang II) or vehicle for 4 weeks; group 2 was injected subcutaneously with deoxycorticosterone (75 mumol/kg once a week) or vehicle for 4 weeks; group 3 consisted of uninephrectomized rats on high sodium intake given deoxycorticosterone or vehicle; and group 4 consisted of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Active and total kallikrein activity was measured in abdominal aortic homogenates using an amidolytic assay. Ang II increased systolic blood pressure at a dose of 400 nmol/kg per day (146 +/- 6 versus 123 +/- 3 mm Hg in controls, P < .01) but not at 80 nmol/kg per day. Deoxycorticosterone did not increase blood pressure except in uninephrectomized rats on high salt (173 +/- 6 versus 135 +/- 4 mm Hg in controls, P < .01). Blood pressure averaged 194 +/- 2 mm Hg in SHR and 123 +/- 3 mm Hg in WKY rats. Vascular kallikrein was similar in rats given Ang II or vehicle. In deoxycorticosterone-treated rats total kallikrein was higher than in controls (9.2 +/- 0.8 versus 3.5 +/- 0.1 pkat/mg protein, P < .05), whereas active kallikrein did not differ (0.09 +/- 0.04 versus 0.09 +/- 0.03 pkat/mg protein, P = NS). A similar pattern was observed in uninephrectomized deoxycorticosterone-treated rats (active, 0.09 +/- 0.03 versus 0.10 +/- 0.04, P = NS; total, 7.4 +/- 0.7 versus 4.1 +/- 0.2 pkat/mg protein, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Guanine nucleotide-binding proteins in aortic smooth muscle from hypertensive rats.
Authors: Li P , Zou A P , al-Kayed N J , Rusch N J , Harder D R
Published: June 2012

To explore the hypothesis that altered vascular muscle signal transduction may underlie some of the vascular changes observed in hypertensive models, we measured expression of GTP-binding protein (G protein) alpha-subunits, Gs, G(i), and Gq, in aortic muscle of reduced renal mass and sham-operated rats and proximal and distal aortic segments from rats with interrenal aortic coarctation (IR-AC). G protein expression was measured by immunoblot analysis. When we probed aortic muscle membrane with G(i) and Gq alpha-subunit antibodies, we identified 41- and 42-kD immunoreactive proteins, respectively. Three immunoreactive bands specific to Gs alpha-subunit antibody were resolved. Immunoreactive blot densities were compared. In aortic muscle membrane of reduced renal mass rats (blood pressure, 148 +/- 7 mm Hg), we found significantly reduced Gs and G(i) blot densities compared with sham-operated controls (blood pressure, 99 +/- 12 mm Hg). There were no differences in Gq blot densities between reduced renal mass and control rats. Gs and G(i) blot densities were significantly lower in IR-AC proximal aortic segments (carotid pressure, 165 +/- 5 mm Hg) and distal aortic segments (femoral pressure, 121 +/- 4 mm Hg) than in aortas of sham-operated controls. In contrast, Gq expression was significantly increased in the high-pressure proximal aortic segments compared with low-pressure distal aortic segments from IR-AC rats. Thus, altered G protein expression occurs in aortic muscle from nongenetic rat models of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Furosemide elicits nonuniform reflex responses via cardiac sympathetic afferents.
Authors: Petersen J S , DiBona G F
Published: June 2012

To examine whether furosemide elicits a cardiorenal reflex response via stimulation of cardiac afferents, furosemide was administered intrapericardially in sinoaortic denervated rats. The role of vagal afferents was evaluated by intrapericardial (IPC) administration of furosemide before and after bilateral vagotomy. The role of cardiac sympathetic afferents was examined by IPC administration of furosemide before and after IPC lidocaine blockade in rats with bilateral vagotomy. Low-dose furosemide (10 micrograms) elicited renal sympathoinhibition, whereas high-dose furosemide (1000 micrograms) produced a rapid and transient change in efferent renal sympathetic nerve activity of either inhibitory (19/49, or 39%) or excitatory (30/49, or 61%) nature. The responses were not affected by vagotomy but were abolished by IPC lidocaine blockade. In rats with a renal sympathoinhibitory response to IPC administration of 1000 micrograms furosemide, both the hypotensive and sympathoinhibitory responses were inhibited by indomethacin, whereas indomethacin did not affect reflex responses in rats showing a renal sympathoexcitatory response to IPC injection of 1000 micrograms furosemide. We conclude that furosemide elicits a nonuniform reflex response mediated via cardiac sympathetic afferents of which the renal sympathoinhibitory response is dependent on intact cyclooxygenase function.
Enhanced vascular reactivity to mastoparan, a G protein activator, in genetically hypertensive rats.
Authors: Kanagy N L , Webb R C
Published: June 2012

Vascular smooth muscle from stroke-prone spontaneously hypertensive rats has an increased responsiveness to the vasoconstrictors angiotensin II and serotonin. This abnormality is postulated to contribute to the hypertension characteristic of this strain of rats. We hypothesized that a portion of the increased responsiveness may be due to altered function of G proteins. This hypothesis was tested using mastoparan, a peptide that mimics ligand-bound receptors to stimulate G proteins directly. In addition, we investigated the mechanism of mastoparan-induced contraction of vascular smooth muscle. Changes in isometric tension were recorded in denuded carotid artery strips from hypertensive and normotensive (Wistar-Kyoto) rats. Vascular strips from the hypertensive rats had a significantly greater response to mastoparan at all concentrations between 10(-8) and 10(-5) mol/L. A G protein inhibitor, N-ethylmaleimide (10(-3) mol/L), attenuated the response to mastoparan (10(-7) mol/L) (67 +/- 4% of control response), whereas pertussis toxin treatment did not. Inhibition of phospholipase C also significantly decreased the mastoparan-induced response (23 +/- 12% of control), and nifedipine (10(-3) mol/L), a calcium channel blocker, completely blocked the mastoparan-induced contraction. Indomethacin treatment did not affect the mastoparan contraction even though mastoparan has been shown to stimulate phospholipase A2 in other cell types. In conclusion, we observed an increased response in carotid arteries from genetically hypertensive rats to a pharmacological intervention that appears to act via G protein-linked phospholipase C stimulation and L-type calcium channel activation, suggesting that the increased vascular reactivity in stroke-prone spontaneously hypertensive rats is due in part to altered function of G proteins.
Nitrosyl factors mediate active neurogenic hindquarter vasodilation in the conscious rat.
Authors: Davisson R L , Johnson A K , Lewis S J
Published: June 2012

Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the "defense reaction". In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation-mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 micrograms/kg i.v.) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid.
Authors: Weintraub N L , Joshi S N , Branch C A , Stephenson A H , Sprague R S , Lonigro A J
Published: June 2012

Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KCl, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinin-induced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 mumol/L) were moderately attenuated by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 mumol/L), whereas when precontracted with KCl, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontracted with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KCl. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 mumol/L) and 4-bromophenacyl bromide (10 mumol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 mumol/L] and nafazatrom [20 mumol/L]) and cytochrome P-450 (proadifen [10 mumol/L] and clotrimazole [10 mumol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways.
Beta-adrenergic blocking treatment and 24-hour baroreflex sensitivity in essential hypertensive patients.
Authors: Parati G , Mutti E , Frattola A , Castiglioni P , di Rienzo M , Mancia G
Published: June 2012

We dynamically evaluated the effects of beta-blockade on the sensitivity of arterial baroreflex control of heart rate in 10 mild or moderate essential hypertensive patients in whom blood pressure was recorded intra-arterially for 24 hours in ambulatory conditions. Twenty-four-hour baroreflex sensitivity was assessed by both (1) a time-domain approach based on the calculation of the slope of the regression line between linearly related progressive increases in systolic blood pressure and pulse interval (+PI/+SBP sequences) and decreases in systolic blood pressure and pulse interval (-PI/-SBP sequences) and (2) a frequency-domain approach, ie, the ratio between the spectral powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha coefficient). Data were obtained before and after 1 month of administration of either acebutolol (n = 5) or labetalol (n = 5). Before treatment, the 24-hour average slopes of the +PI/+SBP and -PI/-SBP sequences were 4.36 +/- 0.32 and 4.05 +/- 0.27 ms/mm Hg, respectively, while the alpha coefficient was 7.78 +/- 0.7 ms/mm Hg. After beta-blockade, these values were increased by 25.3 +/- 6.8%, 25.0 +/- 8.0%, and 32.1 +/- 9.3%, respectively (P < .01 for all values). Thus, beta-blockers potentiate baroreflex sensitivity in daily life. Time-domain and frequency-domain methods yielded superimposable results in dynamically evaluating 24-hour baroreflex sensitivity and its changes after beta-blockade.
In vitro perfusion studies of human resistance artery function in essential hypertension.
Authors: Falloon B J , Heagerty A M
Published: June 2012

To simulate in vivo conditions as closely as possible to in vitro conditions, we examined the morphological and functional characteristics of isolated human subcutaneous small arteries from 17 essential hypertensive patients and 14 normotensive control subjects using a perfusion myograph. Vessel segments were cannulated and exposed to conditions of constant flow and pressure. The ratio of media thickness to lumen diameter in arteries from hypertensive patients increased significantly. With the endothelium intact, sensitivity to extraluminally applied norepinephrine was not different, and this was not affected by inhibition of neuronal amine uptake with cocaine. After removal of the endothelium, sensitivity to norepinephrine was augmented in normotensive vessels to a greater extent than in hypertensive vessels. Endothelium-dependent relaxation to acetylcholine was significantly reduced in arteries from hypertensive patients, but endothelium-independent relaxation to sodium nitroprusside was not different from that observed in vessels from normotensive control subjects. These data demonstrate that sensitivity to exogenous norepinephrine is not different in essential hypertension but that there is defective endothelium-dependent dilatation, suggesting a contributory role for endothelium dysfunction in human essential hypertension.
Forearm blood flow reserve and cardiac and renal indexes of pressure load in normotensive and hypertensive individuals.
Authors: Pedrinelli R , Catapano G , Dell'Omo G , Melillo E , Talarico L , Di Muro C , Giampietro O , Carmassi F , Giusti C , Di Bello V
Published: June 2012

In response to hypertension, arterioles remodel their structure, the heart develops myocardial hypertrophy, and the kidney reduces creatinine clearance and increases albuminuria. To better understand the interrelations among the target organs involved in hypertension, we evaluated minimal forearm vascular resistances--a hemodynamic index of arteriolar structure derived from mean blood pressure and maximal postischemic forearm blood flow--the echocardiographic indexes of cardiac structure, and urinary albumin excretion and creatinine clearance in 29 male mild to moderate non-macroalbuminuric essential hypertensive patients on no drugs and 11 age- and sex-matched normotensive control subjects. Minimal forearm resistances were elevated in hypertensive patients and correlated with left ventricular mass, wall thickness, and mean arterial pressure. Patients with abnormal minimal forearm resistances (2 SD above normal) were characterized by higher pressure, greater wall thickness, lower creatinine clearance, and higher albumin excretion, suggesting that maximal forearm flow capacity does relate to the hemodynamic load exerted on both the kidney and heart. However, the correlation with cardiac structure and mean arterial pressure explained only part of the variability of minimal forearm resistances. Furthermore, no correlation among these parameters was found when hypertensive patients were evaluated separately from normotensive subjects, possibly because of heterogeneous factors active on arteriolar structure and unrelated to the pressor load. Overall, the data suggest that the development of abnormal minimal forearm resistances in the course of the hypertensive process is related to the pressor load, but its details need further understanding.
Endothelin-1 in cerebrospinal fluid in elderly patients with hypertension and dementia.
Authors: Nakajima M , Morimoto S , Takamoto S , Kitano S , Fukuo K , Onishi T , Ogihara T
Published: June 2012

Endothelin-1, a potent endothelium-derived vasoconstrictive peptide, is also known to exist in the central nervous system. We determined endothelin-1-like immunoreactivity in cerebrospinal fluid by a radioimmunoassay in 32 normotensive or hypertensive elderly subjects (79 +/- 8 years old) with or without multi-infarction dementia. The mean value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) elevated in subjects with essential hypertension (> or = 160/95 mm Hg, n = 5, 79 +/- 9 years old) compared with those with borderline hypertension (140-159/90-94 mm Hg, n = 4, 78 +/- 5 years old) and normotensive subjects (< 140/90 mm Hg, n = 23, 79 +/- 8 years old). The value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) positively correlated with both systolic (r = .38) and diastolic (r = .42) blood pressures in all subjects. On the other hand, mean values of endothelin-1-like immunoreactivity in cerebrospinal fluid were also significantly (P < .05) elevated in the groups of patients with multi-infarction dementia that had profoundly decreased Mini-Mental State scores (< or = 10, n = 6) and moderately decreased Mini-Mental State scores (11 to 20, n = 14) compared with those values in subjects with normal cognitive function (score for Mini-Mental State > or = 21, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo effect of calcitriol on calcium transport and calcium binding proteins in the spontaneously hypertensive rat.
Authors: Roullet C M , Roullet J B , Martin A S , McCarron D A
Published: June 2012

The abnormal intestinal Ca2+ transport reported in spontaneously hypertensive rats (SHR) has been attributed to decreased responsiveness to calcitriol. We reexamined this hypothesis by studying the calcitriol regulation of SHR duodenal calbindin-D9K and calmodulin and the relation of calcitriol to Ca2+ uptake by isolated enterocytes. SHR and normotensive Wistar-Kyoto (WKY) rats were injected with either 50 ng/d calcitriol (vit-D) or vehicle alone (control) for 3 days. Decreased calbindin-D9K (P < .001) and cellular Ca2+ flux (P < .001) were observed in control SHR. Calcitriol increased total cell and brush border calbindin-D9K (P < .0001); this variation paralleled plasma calcitriol levels in both strains. In contrast, Ca2+ flux, which increased in vit-D animals, remained lower in SHR for plasma calcitriol levels similar to those in WKY rats. Immunoreactive calmodulin was similar in both strains whether assayed in total cell or brush border membranes. In contrast, when measured by ligand blotting (45Ca), calmodulin was lower in SHR than in WKY rats (P < .01), suggesting the existence of a calmodulin pool with reduced Ca2+ binding capacity in the hypertensive strain. Calcitriol had no effect on calmodulin in either strain. In conclusion, Ca2+ binding protein regulation by calcitriol is normal in the SHR, and decreased hormone responsiveness cannot account for the defective duodenal calcium transport of this experimental model of hypertension.
Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system.
Authors: Kumagai K , Suzuki H , Ichikawa M , Jimbo M , Murakami M , Ryuzaki M , Saruta T
Published: June 2012

To investigate whether changes in renal blood flow induced by nondepressor doses of L-arginine, the precursor of nitric oxide, are mediated by a sympathetic neural mechanism, we examined the following in conscious rabbits: (1) the effects of intravenous infusion of L- or D-arginine (15 to 200 mumol/kg per minute) on renal blood flow and renal sympathetic nerve activity with or without intravenous infusion of a nonpressor dose of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, and (2) the effects of L-arginine on renal blood flow after renal denervation with or without L-NMMA pretreatment. In renal innervated rabbits, L-arginine (100 and 200 mumol/kg per minute) increased renal blood flow by 9 +/- 2 and 16 +/- 3 mL/min (P < .05, respectively) and decreased renal sympathetic nerve activity by 12 +/- 4% and 19 +/- 3% of control (P < .05, respectively). In contrast, no changes occurred in any variable during D-arginine infusion. L-NMMA attenuated the renal blood flow and renal sympathetic nerve activity responses to L-arginine (P < .05). In renal denervated rabbits, L-NMMA also attenuated the renal blood flow responses to L-arginine (P < .05) and abolished them (P < .05) compared with those in renal innervated rabbits. All renal blood flow responses to L-arginine were accompanied by parallel changes in plasma L-citrulline concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Phosphoramidon-sensitive conversion of big endothelin-1 and degradation of endothelin-1 in rat kidney.
Authors: Fujita K , Matsumura Y , Kita S , Hisaki K , Takaoka M , Morimoto S
Published: June 2012

We investigated the intrarenal conversion of big endothelin-1 (ET-1) to ET-1 in the isolated perfused rat kidney. Big ET-1 caused a concentration-dependent increase in perfusion pressure, and the pressor molar potency of the peptide was 50-fold less than that of ET-1. The big ET-1 (2 x 10(-8) mol/L)-induced pressor action was accompanied by increases in immunoreactive endothelin levels in both the perfusate and renal tissues. Phosphoramidon (10(-4) mol/L), a metalloproteinase inhibitor, significantly suppressed the big ET-1-induced pressor action and the accumulation of immunoreactive endothelin in renal tissues. On the other hand, phosphoramidon slightly but significantly sustained the ET-1-induced pressor effect. The effect of kelatorphan (10(-4) mol/L), a specific inhibitor of neutral endopeptidase 24.11, on the ET-1-induced pressor effect was the same as that seen with phosphoramidon. When ET-1 was exogenously added to the perfusate, phosphoramidon or kelatorphan significantly increased the immunoreactive endothelin levels in renal tissues after perfusion, without affecting the disappearance rate of immunoreactive endothelin from the perfusate. Therefore, the phosphoramidon-sensitive ET-1-converting enzyme in the kidney seems to contribute to the functional local conversion of big ET-1 to ET-1, and neutral endopeptidase 24.11 may be responsible for the proteolytic degradation of ET-1 in the kidney. In addition, immunoreactive endothelin levels in renal tissues but not in the perfusate can account for the functional conversion of big ET-1 to ET-1 and for the local proteolytic degradation of ET-1 in the kidney.
Differential regulation of vascular angiotensin I-converting enzyme in hypertension.
Authors: Fernández-Alfonso M S , Kreutz R , Zeh K , Liu Y , Ganten D , Paul M
Published: June 2012

The angiotensin I-converting enzyme (ACE) gene is found on the locus that has been linked to high blood pressure after sodium loading in rats, so in the present study we investigated the role of vascular ACE for the pathophysiology of hypertension in the corresponding parental strains, Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP), in basal conditions at different ages and after sodium loading. Blood pressure was already significantly enhanced in SHRSP from 4 weeks of age, and sodium loading induced an additional increase only in the hypertensive strain. In the aorta, basal ACE gene expression, analyzed by quantitative polymerase chain reaction, and ACE activity were similar in both strains, whereas mRNA levels were elevated in SHRSP after salt compared with WKY rats and correlated with an increase in enzymatic activity. In mesenteric arteries, ACE mRNA levels were significantly enhanced in SHRSP at all ages, although ACE activity was not different between the strains. These results were not modified after sodium loading. These data demonstrate that the level of ACE activity in plasma and vascular tissue can be controlled in a different manner within a rat strain and that in contrast to the soluble form, the membrane-bound ACE may be the one responsible for determining the vasoactive effects of angiotensin II. In addition, ACE undergoes a different regulation in vascular tissues of SHRSP compared with WKY rats, which might be involved in the regulation of blood pressure in these animals.
Differential regulation of natriuretic peptide receptor activity in vascular cells.
Authors: Cao L , Zlock D W , Gardner D G
Published: June 2012

We studied the regulation of the individual natriuretic peptide receptor subtypes by 12-O-tetradecanoylphorbol 13-acetate (TPA) and forskolin in cultured bovine aortic endothelial and smooth muscle cells. In cultured endothelial cells, 10(-8) mol/L TPA caused a reduction in atrial natriuretic peptide (ANP) receptor binding activity that was seen as early as 2 hours after the treatment and reached a maximum (88 +/- 3% of control) after 24 hours, whereas the inhibition of ANP-stimulated cyclic GMP (cGMP) accumulation peaked at 2 hours (62 +/- 13% of control) and returned to control levels after 12 hours. After 24 hours of forskolin (10(-4) mol/L) treatment, ANP binding activity fell to 47 +/- 6%, and cGMP accumulation was 52 +/- 11% of control. Northern blot analysis revealed that 10(-8) mol/L TPA suppressed natriuretic peptide C receptor transcript levels, and forskolin increased levels modestly after 24 hours of treatment. Natriuretic peptide A receptor transcript levels remained unchanged by either treatment. In cultured smooth muscle cells, 10(-8) mol/L TPA suppressed ANP binding activity and ANP-stimulated cGMP formation in a fashion similar to that seen in endothelial cells. TPA treatment also resulted in an inhibition of C-type natriuretic peptide-stimulated cGMP production (59 +/- 7% of control); however, this response persisted for as long as 24 hours after addition of the agonist. Treatment with 10(-4) mol/L forskolin produced a time-dependent inhibition of ANP binding activity and did not inhibit cGMP production stimulated by either ANP or C-type natriuretic peptide. In contrast to the effects seen with endothelial cells, TPA caused a dose-dependent stimulation of natriuretic peptide C receptor mRNA, whereas forskolin was inhibitory in smooth muscle cells. These results indicate that the effects of the kinase activators are a function of the individual receptor subtype as well as the cell in which it is expressed and imply a considerable degree of flexibility in the response to regulatory stimuli.
Insulin resistance, insulin, proinsulin, and ambulatory blood pressure in type II diabetes.
Authors: Pinkney J H , Mohamed-Ali V , Denver A E , Foster C , Sampson M J , Yudkin J S
Published: June 2012

Both insulin resistance and insulin concentrations correlate with blood pressure in nondiabetic subjects, but there is no consensus on these relations in subjects with non-insulin-dependent diabetes, perhaps because of the use of nonspecific insulin assays and clinic blood pressure measurement. Therefore, we have investigated the relation between ambulatory blood pressure, insulin sensitivity (measured by an insulin sensitivity test), and levels of insulin and its principal precursors, measured by specific assays, in 24 subjects with non-insulin-dependent diabetes. Insulin sensitivity (glucose metabolic clearance rate) correlated strongly with mean 24-hour ambulatory systolic blood pressure (r = -.650, P < .001). In contrast, there was no relation between this blood pressure index and fasting levels of insulin (r = .096, P = NS) or all insulin-like molecules (r = .077, P = NS). Dichotomized on 24-hour ambulatory systolic blood pressure levels, the hypertensive group was more insulin resistant than the normotensive group (metabolic clearance rate, 3.6 [0.7] versus 6.5 [3.0] mL.kg-1.min-1, P = .006), whereas there was no difference in insulin or proinsulin concentrations among the groups. In multiple regression analysis, insulin sensitivity was the major determinant of blood pressure. We conclude that in subjects with non-insulin-dependent diabetes mellitus, blood pressure is related to insulin sensitivity but not to fasting levels of insulin, suggesting that hyperinsulinemia is probably not the mediator of this relation.
Role of metabotropic glutamate receptors in ventrolateral medulla of hypertensive rats.
Authors: Tsuchihashi T , Abe I , Fujishima M
Published: June 2012

Evidence is accumulating for the role of metabotropic, as well as ionotropic, glutamate receptors in cardiovascular regulation. We sought to determine whether stimulation of metabotropic glutamate receptors in the rostral ventrolateral medulla would evoke enhanced cardiovascular responses in spontaneously hypertensive rats (SHR). Thus, we microinjected (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic glutamate receptors, into the rostral ventrolateral medulla of urethane-anesthetized adult SHR and age-matched Wistar-Kyoto (WKY) rats. Microinjection of (1S,3R)-ACPD (1 nmol/50 nL) produced increases in mean arterial pressure and splanchnic sympathetic nerve activity in SHR (+41 +/- 6 mm Hg and +34 +/- 4%, respectively) that were significantly greater than those observed in WKY rats (+18 +/- 3 mm Hg and +22 +/- 3%, P < .005 and P < .05, respectively). The pressor responses evoked by microinjection of L-glutamate (2 nmol), N-methyl-D-aspartate (20 pmol), or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol) were also significantly (P < .001) augmented in SHR (+55 +/- 3, +61 +/- 7, and +53 +/- 5 mm Hg, respectively, in SHR versus +31 +/- 1, +30 +/- 3, and +28 +/- 2 mm Hg in WKY rats). Results indicate that stimulation of metabotropic, as well as ionotropic, glutamate receptors in the rostral ventrolateral medulla evokes enhanced cardiovascular responses in SHR, which may contribute to hypertension in this model.
Hypertension increases insulin-like growth factor binding protein-4 mRNA levels in rat aorta.
Authors: Anwar A , Delafontaine P
Published: June 2012

Insulin-like growth factor-I (IGF-I) is an endocrine and autocrine/paracrine growth factor. Recently, we have demonstrated that interrenal aortic coarctation in the rat increases IGF-I mRNA levels in the thoracic aorta, consistent with a role for this mitogen in hypertensive vascular remodeling. The effects of IGF-I are modulated by several IGF binding proteins including IGFBP-3, the main circulating carrier of IGF-I, and IGFBP-4, the main IGF binding protein produced by vascular smooth muscle cells in vitro. To obtain insights into the regulation of IGF-I and more specifically to study potential changes in IGF binding proteins in high-renin hypertension, we studied male Sprague-Dawley rats that had undergone abdominal aortic coarctation. Compared with sham-operated rats, the study rats showed a rapid increase in IGFBP-4 mRNA levels in the hypertensive (thoracic) aorta, reaching a plateau at 3 days (2.5-fold increase) and persisting for at least 14 days. In striking contrast, IGFBP-4 mRNA decreased slightly in the normotensive (abdominal) aorta at 14 days. IGFBP-3 mRNA levels did not change in either vascular bed after coarctation. Study of hepatic tissue indicated that in coarcted rats IGFBP-4 and IGFBP-3 mRNA levels decreased transiently (approximately 50% at 7 days compared with sham). Circulating IGF-I in coarcted animals decreased slightly (P = .08), and Western ligand analysis indicated that circulating levels of IGF binding proteins were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium.
Authors: Parmer R J , Stone R A , Cervenka J H
Published: June 2012

Previous studies have suggested striking racial differences in hypertension-related renal disease. To explore potential mechanisms responsible for these differences, we investigated changes in renal hemodynamics in white and black essential hypertensive patients in response to alterations in dietary sodium. Patients were untreated, age-matched, and blood pressure-matched white (n = 59) and black (n = 22) males with essential hypertension. Studies were conducted on an inpatient metabolic ward and included assessment of blood pressure, urinary sodium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow after 5 days each of high and low salt diets. In response to high dietary salt intake, both white and black patients demonstrated significantly higher mean arterial pressure, renal plasma flow, and renal blood flow, and there were no racial differences in the changes in these parameters. However, whites and blacks differed significantly in glomerular filtration rate, with black hypertensive patients showing an increase in glomerular filtration rate (+17.3 +/- 5.3 mL/min per 1.73 m2, F = 7.586, P = .007) and white hypertensive patients showing no change (-0.2 +/- 3.3 mL/min per 1.73 m2) in response to high dietary sodium. These data demonstrate racial differences in the autoregulation of glomerular filtration rate in response to changes in dietary sodium. These differences suggest that glomerular hyperfiltration in response to a high salt diet may be a mechanism contributing to the racial disparity in hypertension-related renal disease.
Natriuretic peptides in the human kidney.
Authors: Totsune K , Takahashi K , Murakami O , Satoh F , Sone M , Saito T , Sasano H , Mouri T , Abe K
Published: June 2012

We studied the presence of three natriuretic peptides--atrial natriuretic peptide (ANP), human brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)--in the human kidney by radioimmunoassay and immunocytochemistry. Immunoreactive ANP, immunoreactive human BNP, and immunoreactive CNP concentrations in six kidneys were 0.12 +/- 0.07 (mean +/- SD), 0.23 +/- 0.08, and 0.37 +/- 0.07 pmol/g wet wt, respectively. Sephadex G-50 superfine column chromatography and reversed-phase high-performance liquid chromatography of kidney extracts revealed a broad peak of immunoreactive ANP comigrating with ANP-28 and urodilatin. Renal immunoreactive human BNP consisted of three components; the major component comigrated with human BNP-32. Renal immunoreactive CNP consisted of at least two components; the major component comigrated with CNP-22, and the minor component eluted in a position similar to that of authentic human CNP-53. Immunocytochemistry showed that immunoreactive human BNP was colocalized with immunoreactive ANP in the segments of distal tubules, whereas immunoreactive CNP was found predominantly in the proximal tubules. These findings indicate that these three natriuretic peptides are present in the human kidney and raise the possibility that they form a renal natriuretic peptide system that participates in the local regulation of sodium and water transport and renal circulation in the human kidney.
Renal Effects of Acute Amino Acid Infusion in Hypertension Induced by Chronic Nitric Oxide Blockade
Authors: Qiu Changbin , Engels Kevin , Samsell Lennie , Baylis Chris
Published: June 2012

Abstract
l
-Arginine is the physiological substrate of nitric oxide, a vasodilator that controls blood pressure and renal hemodynamics in the basal state. In the present studies, we produced chronic nitric oxide blockade by oral administration of the
l
-arginine analogue
N
G
-nitro-
l
-arginine methyl ester, which produced sustained hypertension and increased renal vascular resistance in conscious rats. Acute excess
l
-arginine had little effect on blood pressure but completely normalized renal vascular resistance and increased renal plasma flow in chronically nitric oxide–blocked hypertensive rats. In contrast to
l
-arginine,
d
-arginine had no renal hemodynamic effects in either normal or chronically nitric oxide–blocked rats. Acutely administered glycine was ineffective in vasodilating the chronically nitric oxide–blocked rat kidney, in a dose that produced renal vasodilation in normal rats. These findings indicate the following: (1) Hypertension induced by chronic nitric oxide blockade due to substituted
l
-arginine analogue cannot be acutely reversed with excess L-arginine, suggesting that the maintenance of the hypertension is not solely caused by competitive inhibition of nitric oxide production; (2) in contrast, the kidney remains responsive to
l
-arginine whereas the renal vasodilator response to glycine is abolished in this model of hypertension.
Hypertension After Renal Transplantation
Authors: van der Schaaf Margriet R. , Hené Ronald J. , Floor Marianne , Blankestijn Peter J. , Koomans Hein A.
Published: June 2012

Abstract
We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111±9 and 115±9 mm Hg, respectively;
P
<.05). Blood pressure during both treatments was lower than during placebo (124±12 mm Hg,
P
<.05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10±20%,
P
<.05) and effective renal plasma flow (27±20%,
P
<.01) and a decrease in renal vascular resistance (23±18%,
P
<.01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension.
Insulin and Forearm Vasodilation in Hypertension-Prone Men
Authors: Hulthén U. Lennart , Endre Tomas , Mattiasson Ingrid , Berglund Göran
Published: June 2012

Abstract
Insulin-stimulated peripheral glucose uptake and insulin-mediated forearm vasodilation were investigated in 38 normotensive men with a family history of hypertension (relatives) compared with 27 age- and body mass index–matched normotensive men with no family history of hypertension (control subjects). The euglycemic hyperinsulinemic clamp technique was used to measure peripheral glucose uptake (insulin sensitivity index) and the metabolic clearance rate of insulin. Intra-arterial blood pressure and forearm blood flow were determined simultaneously, and forearm vascular resistance was calculated. The insulin sensitivity index was lower in relatives than in control subjects. The metabolic clearance rate of insulin was reduced and did not correlate to glucose disposal in the relatives as opposed to the control subjects. Forearm blood flow increased and forearm vascular resistance decreased to a similar extent in the two groups during the clamp. The vasodilator response was positively correlated to glucose disposal only in the relatives. In conclusion, impaired insulin-stimulated peripheral glucose uptake in normotensive sons from hypertensive families was accompanied by retained insulin-mediated forearm vasodilation. Thus, skeletal muscle blood flow supply does not seem to be the major determinant for glucose disposal. On the other hand, the positive correlation between glucose disposal and decrease in forearm vascular resistance in the relatives suggests that insulin-mediated vasodilation may be a limiting factor for peripheral glucose uptake in insulin-resistant individuals.
Different Flow Regulation Mechanisms Between Celiac and Mesenteric Vascular Beds in Conscious Rats
Authors: Iida Noriko
Published: June 2012

Abstract
The aims of this study were to elucidate the vasoconstrictor mechanism that mediates the changes in celiac and mesenteric vascular resistances during vasoconstriction and hypotension induced by ganglionic blockade and to explore the preferential mechanism that contributes to the elevation of arterial pressure in conscious spontaneously hypertensive rats (SHR). In conscious SHR and normotensive control rats, blood flow and arterial pressure were measured with an implanted electromagnetic flow probe and an indwelling arterial catheter. Peripheral vascular resistance was calculated as arterial pressure divided by regional flow. Celiac contribution to the hypertension in SHR was below average for the entire body and was smaller than that from the superior mesenteric bed. The increase of mesenteric resistance with arterial pressure elevation after ganglionic blockade suggests that mesenteric blood flow is regulated by a stretch-dependent myogenic mechanism, whereas celiac blood flow is regulated preferentially by the sympathetic neural mechanism. It is speculated that the flow superregulation in the mesenteric bed in SHR is due to the enhanced myogenic response and contributes to the early stage of hypertension.
Attenuated Cardiovascular Response to Adenosine in the Brain Stem Nuclei of Spontaneously Hypertensive Rats
Authors: Tseng Ching-Jiunn , Ger Luo-Ping , Lin Hui-Ching , Tung Che-Se
Published: June 2012

Abstract
We previously reported that adenosine has significant depressor effects in the nucleus tractus solitarii and area postrema of the rat. The purpose of this study was to determine whether the spontaneously hypertensive rat (SHR) has abnormalities in medullary sensitivity to adenosine. Male SHR and Wistar-Kyoto (WKY) rats (aged 12 to 15 weeks) were anesthetized with urethane, and blood pressure was monitored intra-arterially. Stereotaxic microinjection (60 nL) of adenosine was made into the nucleus tractus solitarii and the area postrema and was confirmed histologically. Dose-related decreases in mean blood pressure and heart rate occurred in both strains tested, and this effect was completely abolished by 1,3-dipropyl-8-
p
-sulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist. However, there were significant differences between SHR and WKY rats in the magnitude of blood pressure and heart rate depression. A similar pattern of response was found in the area postrema. Thus, adenosine is a potent depressor agent in the nucleus tractus solitarii and area postrema of rats, and adenosine has significantly fewer depressor effects in SHR. These data suggest that alterations in purinergic mechanisms of central cardiovascular control exist in the SHR model.
Lisinopril Improves Aortic Compliance and Renal Flow
Authors: Shimamoto Hiroyuki , Shimamoto Yoriko
Published: June 2012

Abstract
We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (
P
<.01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (
P
<.01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.
Modulation of the Ca
2+
Pump by the Hypothalamic-Hypophysary Inhibitory Factor
Authors: Ricote Mercedes , García-Martín Elena , Sancho Jose , Gutiérrez-Merino Carlos
Published: June 2012

Abstract
We previously purified to homogeneity an endogenous sodium pump inhibitor from bovine hypothalamus and hypophysis that is different from digoxin or ouabain and studied the effects of this factor on the total Ca
2+
,Mg
2+
-ATPase activity of plasma membrane of synaptosomes. This factor inhibits the calcium pump and the total Mg
2+
-ATPase activity of these membranes with approximately the same
K
0.5
values of inhibition. The potency of this factor as an inhibitor depends on the membrane concentration in the assay medium. The inhibition of the magnesium-dependent ATPase activities of these membranes was of a noncompetitive type with respect to the substrate Mg
2+
-ATP and did not significantly shift the calcium dependence of the Ca
2+
,Mg
2+
-ATPase activity. We suggest that the calcium pump of the synaptosomal plasma membrane is inhibited by this factor through disruption of the lipid annulus; this inhibition could play a role in the control of calcium homeostasis by increasing the cytosolic free calcium concentration.
Physiological Determinants of Hyperreactivity to Stress in Borderline Hypertension
Authors: Sherwood Andrew , Hinderliter Alan L. , Light Kathleen C.
Published: June 2012

Abstract
Blood pressure hyperreactivity during stress is characteristic of borderline hypertension in white men. The present study evaluated the hemodynamic basis of this hyperreactivity and assessed its physiological basis in terms of sympathetic nervous system function. Cardiovascular adjustments to an aversive reaction time test were compared with those of the forehead cold pressor test, representing stressors that elicit active behavioral responses in contrast to passive tolerance of aversive stimulation. As anticipated, blood pressure increases were greater in 12 borderline hypertensive men compared with 21 age-matched normotensive men during the active reaction time stressor but not during the passive cold pressor test. The pressor hyperreactivity in borderline hypertensives was associated with excessive rises in plasma epinephrine and norepinephrine, leading to greater increases in cardiac output, despite evidence that the cardiac β-adrenergic receptors in these subjects were downregulated compared with those of normotensive subjects. During the cold pressor test, borderline hypertension was associated with greater increases in systemic vascular resistance, which, in the presence of normal baroreceptor reflex function, led to an attenuation of cardiac output, thus producing no greater net effect on blood pressure than seen in normotensive subjects. Evidence of vascular hypertrophy in the borderline hypertensive subjects was considered to account for their vascular hyperreactivity to cold pressor stimulation. Collectively, the observations in this study further support the view that the early stages of hypertension in white men are characterized by sympathetic nervous system hyperreactivity, but only in association with tasks that elicit active behavioral coping responses. The extent to which these responses are elicited by typical daily events may be an important determinant of whether borderline hypertension matures to its established form, which displays hemodynamic characteristics dominated by vascular structural changes.