bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of preferentially expressed genes in the kidneys of hypertensive rats.
Authors: Iwai N , Inagami T
Published: June 2012

By differential hybridization, three complementary DNAs designated as S3, S2, and SA were isolated, and the corresponding messenger RNAs (mRNAs) were differentially expressed between the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. S3 is identical to cytochrome P450 IV A2. SA encoded a protein of 546 amino acid residues, and its carboxyl terminal region had a slight homology to luciferase. No homologous sequence has been reported in S2 sequences. S3 mRNA was about four times more abundantly expressed in the kidneys of 28-day-old SHR than in those of age-matched WKY rats, but there was no difference at age 16 weeks. A low NaCl diet positively modulated the expression of the S3 gene. S2 mRNA was almost undetectable in the kidneys of 28-day-old WKY rats but was clearly detected in those of age-matched SHR. The expression level of S2 mRNA in the livers of 16-week-old SHR was about five times higher than that of age-matched WKY rats. The expression of S2 mRNA in the livers was modulated by dietary NaCl and captopril. SA mRNA was more than 10 times more abundantly expressed in the kidneys of SHR than in those of WKY rats from age 4 weeks. With the administration of captopril, the expressions of SA mRNA in the livers of SHR were positively modulated. Because these three genes are not only differentially expressed between SHR and WKY rats but also related to sodium metabolism or blood pressure control, the identification of these genes may provide important probes to examine the mechanisms of hypertension.
Sir Horace Smirk. Pioneer in drug treatment of hypertension.
Authors: Doyle A E
Published: June 2012

Sir Horace Smirk deserves much of the credit for establishing the benefits of reducing blood pressure. He was one of the main early proponents of the idea that it was the raised intra-arterial pressure itself that caused many of the cardiac and vascular complications of hypertension. His training in both pharmacology and internal medicine enabled him to devise practical methods for successful treatment of hypertension with ganglion blocking drugs such as hexamethonium. The major clinical benefits that followed such drug treatment proved a great stimulus to the development of drugs with fewer disadvantages and to widespread acceptance of the beneficial effects of antihypertensive drug treatment.
Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats.
Authors: Hajdu M A , Heistad D D , Baumbach G L
Published: June 2012

The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195 +/- 8 to 125 +/- 5 and 148 +/- 3 mm Hg, respectively [mean +/- SEM]; p less than 0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911 +/- 155 to 1,244 +/- 101 and 1,388 +/- 59 microns 2, respectively, compared with 1,405 +/- 95 microns 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 +/- 6 to 62 +/- 2 mm Hg with cilazapril versus 79 +/- 5 mm Hg for hydralazine compared with 60 +/- 4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 +/- 4 to 100 +/- 4 microns for cilazapril versus 91 +/- 3 microns for hydralazine compared with 107 +/- 3 microns for untreated WKY rats).(ABSTRACT TRUNCATED AT 250 WORDS)
Chemical sympathectomy alters the development of hypertension in miniature swine.
Authors: Thomas G D , O'Hagan K P , Zambraski E J
Published: June 2012

To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6-hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine-treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6-hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6-hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine.
Relation of electrolytes to blood pressure in men. The Yi people study.
Authors: He J , Tell G S , Tang Y C , Mo P S , He G Q
Published: June 2012

The relations of sodium, potassium, calcium, and magnesium to blood pressure were investigated in four groups of men (119 high-mountain Yi farmers, 114 mountainside Yi farmers, 89 Yi migrants, and 97 Han people) with a wide range of electrolyte intake in Puge County, Sichuan Province, People's Republic of China. Electrolytes were measured in diet, serum, and urine. Sodium excretion was 73.9 mmol/24 hr in high-mountain Yi farmers, 117.9 mmol/24 hr in mountainside Yi farmers, 159.4 mmol/24 hr in Yi migrants, and 186.0 mmol/24 hr in the Han people. In ecological correlation analysis, dietary and urinary sodium were significantly and positively correlated with both systolic and diastolic pressure, whereas serum sodium showed no relation with blood pressure. In diet, serum, and urine, potassium was negatively related to systolic and diastolic pressure, whereas the sodium/potassium ratio showed a positive association. With regard to calcium, only urinary excretion was significantly and positively related to blood pressure. No relation was found between magnesium and blood pressure. Analyses at the individual level confirmed the results for sodium and potassium seen at the ecological level, but in addition, dietary calcium and magnesium were significantly and negatively correlated to both systolic and diastolic pressure, and urinary magnesium was inversely related to diastolic pressure. These relations persisted after controlling for age, body mass index (kg/m2), heart rate, alcohol, and total energy intake in multiple regression analysis performed separately for electrolytes in diet, serum, and urine. In multiple regression analysis, an increase in sodium intake of 100 mmol/day corresponded to an increase of 2.3 mm Hg systolic blood pressure and 1/8 mm Hg diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
High density lipoprotein turnover in patients with hypertension.
Authors: Chen Y D , Sheu W H , Swislocki A L , Reaven G M
Published: June 2012

Although hyperinsulinemia and decreased high density lipoprotein cholesterol concentration can occur in patients with hypertension, there is no information available concerning the dynamic state of high density lipoprotein metabolism. To address this issue, we quantified high density lipoprotein turnover in 12 patients with mild hypertension and 11 matched subjects with normal blood pressure. Patients with high blood pressure had lower high density lipoprotein cholesterol concentrations. Fractional catabolic rates of 125I-apolipoprotein AI (apoAI)/high density lipoprotein were faster in patients with hypertension (0.36 +/- 0.02 versus 0.26 +/- 0.02 l/day, p less than 0.001). Total synthetic rates of apoAI were also significantly greater in patients with high blood pressure (17.4 +/- 1.1 versus 13.2 +/- 0.6 mg/kg/day, p less than 0.001). Although significant correlation was observed between blood pressure and fractional catabolic rate of 125I-apoAI/high density lipoprotein in the experimental population (r = 0.52, p less than 0.01), no relation was found when patients with normal blood pressure or hypertension were considered separately. However, a highly significant positive correlation was found between 125I-apoAI/high density lipoprotein fractional catabolic rate and insulin concentration in the entire population (r = 0.72, p less than 0.001). In conclusion, the patients with mild hypertension studied were hyperinsulinemic, had a faster fractional catabolic rate of 125I-apoAI/high density lipoprotein, and a lower high density lipoprotein-cholesterol concentration. It is suggested that the changes seen in high density lipoprotein-cholesterol concentration and 125I-apoAI/high density lipoprotein fractional catabolic rates were secondary to the hyperinsulinemia and not due to the high blood pressure per se.
In vitro tissue potencies of converting enzyme inhibitors. Prodrug activation by kidney esterase.
Authors: Grima M , Welsch C , Michel B , Barthelmebs M , Imbs J L
Published: June 2012

The inhibition of angiotensin converting enzyme by ramipril, ramiprilat, enalapril, enalaprilat, and captopril was studied in the plasma and various tissues (lung, heart, renal cortex, renal medulla) of normotensive rats and spontaneously hypertensive rats. Displacement curves for [3H]ramiprilat were established on each tissue with the converting enzyme inhibitors, and their potencies were expressed as the concentration that inhibited 50% of the specific [3H]ramiprilat binding. In the plasma, lung, and heart, the order of activities was: ramiprilat greater than enalaprilat greater than captopril greater than ramipril greater than enalapril. This order was different in the kidney (cortex and medulla): ramiprilat greater than enalaprilat greater than ramipril greater than captopril greater than enalapril. For ramiprilat, enalaprilat, and captopril, there were no differences in their respective potencies between tissues or between rat strains. However, the two prodrugs ramipril and enalapril were 10-30 times more active in the kidney than in the other tissues in both groups of rats. This was due to the deesterification of the prodrugs: in the presence of an esterase inhibitor (diethyl nitrophenyl phosphate, 10 microM), the potencies of ramipril in the kidney were not different from that obtained in the lung, which was not affected by the presence of the esterase inhibitor. These results suggest that the variations in the tissue activities of an angiotensin converting enzyme inhibitor are probably not due to differences in tissue affinities of the angiotensin converting enzyme inhibitor but depend on the concentration of this angiotensin converting enzyme inhibitor in each tissue.
Renal and endocrine responses to a renin inhibitor, enalkiren, in normal humans.
Authors: Cordero P , Fisher N D , Moore T J , Gleason R , Williams G H , Hollenberg N K
Published: June 2012

Interpretation of renin-angiotensin blockade with angiotensin converting enzyme inhibitors is potentially confounded by their multiple effects. We used a selective renin inhibitor (enalkiren, A-64662) to explore the renal and endocrine effects of angiotensin II in healthy men. Each received 90-minute enalkiren infusions at 2-day intervals, on a low (10 mmol, 16 subjects) and high (200 mmol, 12 subjects) salt diet. Plasma renin activity, immunoreactive plasma angiotensin II and aldosterone concentrations, inulin, and p-aminohippurate clearance were measured by standard methods. Plasma renin activity fell at 0.1 micrograms/kg, but the threshold for biologic effect was 256 micrograms/kg, where plasma immunoreactive angiotensin II and aldosterone concentration fell, and renal plasma flow rose (p less than 0.01). The maximal renal vascular response (+152 +/- 23 ml/min/1.73 m2) occurred at 512 micrograms/kg (p less than 0.01). Diastolic and mean blood pressure fell modestly but significantly (p less than 0.05). Responses were limited on a high salt diet. We confirm that conventional plasma renin activity measurement is misleading in humans receiving a renin inhibitor. The renal vascular response to renin inhibition in this study appeared to substantially exceed reported responses to angiotensin converting enzyme inhibition, perhaps reflecting a crucial and relatively inaccessible intrarenal locus.
Role of prostanoids in renin-dependent and renin-independent hypertension.
Authors: Lin L , Mistry M , Stier C T , Nasjletti A
Published: June 2012

We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms.
Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study.
Authors: Wikstrand J , Warnold I , Tuomilehto J , Olsson G , Barber H J , Eliasson K , Elmfeldt D , Jastrup B , Karatzas N B , Leer J
Published: June 2012

The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown.
Agonist-sensitive calcium stores in arteries from steroid hypertensive rats.
Authors: Perry P A , Webb R C
Published: June 2012

The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites.
Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism.
Authors: Griffin S A , Brown W C , MacPherson F , McGrath J C , Wilson V G , Korsgaard N , Mulvany M J , Lever A F
Published: June 2012

Angiotensin II, when given in low doses, raises blood pressure slowly. When tested in vitro on vascular smooth muscle cells, it has mitogenic and trophic effects; it is not known if it has these effects in vivo. Our purpose was to determine whether vascular hypertrophy develops during slow pressor infusion of angiotensin II and, if so, whether it is pressure induced. Three experiments were done in rats infused subcutaneously with angiotensin II (200 ng/kg/min) by minipump for 10-12 days. Experiment 1: Angiotensin II gradually raised systolic blood pressure (measured in the tail) from 143 +/- 2 to 208 +/- 8 mm Hg (mean +/- SEM), significantly suppressing plasma renin and increasing threefold (NS) plasma angiotensin II. There was no loss of peptide in the pump infusate when tested at the end of the experiment. Experiment 2: In the perfused mesenteric circulation, vasoconstrictor responses to norepinephrine, vasopressin, and KCl were enhanced in rats given a slow pressor infusion of angiotensin II, but sensitivity of responses was not altered. This combination of changes suggests that vascular hypertrophy develops during slow pressor infusion of angiotensin II. Experiment 3: Vessel myography was done after angiotensin II infusion with and without a pressor response. Angiotensin II raised systolic blood pressure, increased heart weight, and produced myographic changes of vascular hypertrophy in the mesenteric circulation, increasing media width, media cross-sectional area, and media/lumen ratio. Hydralazine given with angiotensin II prevented the rise of pressure and the cardiac effect but not the vascular changes. Two-way analysis of variance showed that angiotensin II significantly increased media width, media cross-sectional area, and media/lumen ratio, all independent of hydralazine. Thus, although hydralazine inhibits the pressor and cardiac effects of angiotensin II, suggesting a pressor mechanism for the cardiac change, it does not inhibit structural vascular change, which suggests that at least part of the effect has a non-pressor mechanism.
Endothelium-derived relaxing factor modulates endothelin action in afferent arterioles.
Authors: Ito S , Juncos L A , Nushiro N , Johnson C S , Carretero O A
Published: June 2012

Endothelin is a potent vasoconstrictor, whereas endothelium-derived relaxing factor (EDRF) is a potent vasodilator. Both are produced by the endothelium. Although they have been studied extensively in large vessels, little is known about their actions in renal microvessels. Using microdissected rabbit afferent arterioles, we studied the vascular response to synthetic endothelin and its interaction with EDRF and the effect of endothelin on renin release. Afferent arterioles were either microperfused in vitro at 60 mm Hg to measure luminal diameter or incubated without microperfusion to assess renin release. When added to the bath, 10(-10) or 10(-9) M endothelin decreased the diameter by 32 +/- 8% (n = 7, p less than 0.01) or 76 +/- 7% (p less than 0.0001), respectively. Pretreatment with Nw-nitro L-arginine, which inhibits synthesis of EDRF, decreased basal diameter by 15 +/- 1% (p less than 0.001) and augmented endothelin-induced constriction; decrease in diameter with 10(-10) M endothelin was 78 +/- 10% (n = 4, p less than 0.01 versus nontreated). In afferent arterioles preconstricted by endothelin, acetylcholine at concentrations of 10(-8) to 10(-5) M increased the diameter in a dose-dependent manner. Basal renin release was 0.62 +/- 0.15 ng angiotensin I/hr/afferent arterioles/hr (n = 13) and was not affected by endothelin (10(-10) to 10(-6) M). Increase in renin release by isoproterenol was the same in afferent arterioles pretreated with vehicle or endothelin (10(-7) M; delta, 0.49 +/- 0.21 versus 0.42 +/- 0.19; n = 13).(ABSTRACT TRUNCATED AT 250 WORDS)
Dual hemodynamic mechanisms for salt-induced hypertension in Dahl salt-sensitive rats.
Authors: Simchon S , Manger W M , Brown T W
Published: June 2012

Cardiac output, blood volume, total peripheral resistance, and renal blood flow were measured in awake salt-sensitive and salt-resistant Dahl rats on normal rat chow (1% NaCl) and on high salt (8% NaCl) diets. Rats were studied after 4, 8, and 46 weeks on a 1% NaCl diet and after 4 and 8 weeks on an 8% NaCl diet. Salt-sensitive rats on 8% NaCl for 4 weeks developed systolic hypertension; by 8 weeks they developed greater systolic and also diastolic hypertension. Salt-resistant rats on 8% NaCl remained normotensive throughout the studies, although renal resistance decreased (p less than 0.05). At 4 weeks, hypertension in salt-sensitive rats on 8% NaCl was caused by increased blood volume and cardiac output (p less than 0.05), with normal total peripheral resistance. At 8 weeks, hypertension was due to increased total peripheral resistance (p less than 0.05); cardiac output was below normal despite persistent elevation of blood volume (p less than 0.05). Salt-sensitive rats on 1% NaCl for 46 weeks were hypertensive, with elevated total peripheral resistance (p less than 0.05); cardiac output decreased (p less than 0.05), whereas blood volume remained unchanged. Salt-resistant rats on 1% NaCl remained normotensive with no charges in hemodynamics. Salt-sensitive rats on 8% NaCl for 4 weeks had an increase in renal vascular resistance but no significant change in nonrenal resistance or total peripheral resistance. The increased total peripheral resistance in salt-sensitive rats on 8% NaCl for 8 weeks and on 1% NaCl for 46 weeks was a reflection of increases of both renal and nonrenal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Androgen receptor and the testes influence hypertension in a hybrid rat model.
Authors: Ely D L , Salisbury R , Hadi D , Turner M , Johnson M L
Published: June 2012

The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males.(ABSTRACT TRUNCATED AT 250 WORDS)
Patterns of sodium excretion during sympathetic nervous system arousal.
Authors: Harshfield G A , Pulliam D A , Alpert B S
Published: June 2012

The purpose of this study was to examine Na+ handling and regulation during 1 hour of behaviorally induced sympathetic nervous system (SNS) arousal followed by 2 hours of recovery. Two patterns of response were observed among experimental subjects, despite similar changes in blood pressure and heart rate. In one group (n = 19), Na+ excretion increased significantly during SNS arousal, which then decreased significantly during recovery (12.3 versus 16.0 versus 13.1 meq/hr, baseline, SNS arousal, recovery, respectively). Changes in Na+ excretion were correlated with changes in creatinine clearance from baseline to SNS arousal (r = 0.54) and SNS arousal to recovery (r = 0.58), and were accompanied by significant increases in plasma renin activity (1.5 versus 2.0 ng/ml/hr) and aldosterone (8.5 versus 10.3 ng/ml/hr) from baseline to SNS arousal. Na+ excretion decreased during SNS arousal in the other group of subjects (n = 17) and remained below baseline levels during recovery (16.2 versus 12.7 versus 11.9 meq/hr). These changes were associated with significant decreases in creatinine clearance from baseline to recovery (138 versus 121 ml/min/1.73 m2) and significant increases in plasma renin activity from baseline to SNS arousal (1.3 versus 2.2 ng/ml/hr) but not in aldosterone. Control subjects (n = 24) maintained baseline levels of each variable throughout the procedure. These results suggest that individuals differ in Na+ handling and regulation during behavioral arousal. Decreases in Na+ have been reported previously in humans and animals at risk for the development of hypertension.
Sympathetic neural control of vascular muscle in reduced renal mass hypertension.
Authors: Stekiel W J , Contney S J , Lombard J H
Published: June 2012

Vascular smooth muscle (VSM) transmembrane potentials (Em) were measured in situ in small branch arteries (150-300-microns o.d.), small branch veins (300-400-microns o.d.), arterioles (90-150-microns o.d.), and venules (80-250-microns o.d.) in the mesenteric and gracilis muscle and the arterioles and venules of cremaster muscle vascular beds in anesthetized rats with reduced renal mass hypertension (HT-RRM) and normotensive sham-operated RRM control rats. All rats were given a 4% NaCl diet for 2 weeks with water ad libitum. Relative to sham, HT-RRM mesenteric and gracilis arterial and venous vessels, but not the microvessels of the cremaster muscle bed, were less polarized during superfusion with normal physiological salt solution. Also relative to sham, hyperpolarization responses to local sympathetic neural (SNS) denervation with 6-hydroxydopamine were greater in mesenteric and gracilis small arteries, arterioles, veins, and venules but not in cremaster microvessels. The immediate (less than 5-minute) electrogenic depolarization response to local blockade of VSM Na(+)-K+ pump activity with 10(-3) M ouabain was similar between each respective HT-RRM and sham vessel pair in each vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Central effect of endothelin on neurohormonal responses in conscious rabbits.
Authors: Matsumura K , Abe I , Tsuchihashi T , Tominaga M , Kobayashi K , Fujishima M
Published: June 2012

It has been shown that endothelin-1 (ET-1) binding sites exist in the central nervous system and that the injection of intracerebroventricular ET-1 induces a pressor response. Therefore, we determined the neurohormonal and cardiovascular responses to intracerebroventricular ET-1 (25 pmol/kg) in conscious rabbits with chronically instrumented electrodes on the renal sympathetic nerve. Intracerebroventricular ET-1 provoked a prompt increase in arterial pressure and in renal sympathetic nerve activity within 5 minutes, and peak values were obtained at 20 and 40 minutes, respectively. Plasma epinephrine and norepinephrine reached peak values at 5-20 minutes. Plasma vasopressin and plasma glucose levels also increased significantly, but plasma osmolality, hematocrit, and serum sodium and potassium concentrations did not show any changes. Arterial blood gas analysis showed respiratory alkalosis. However, pretreatment with intravenous pentolinium (5 mg/kg), a ganglion blocking agent, abolished these neurohormonal and cardiovascular responses. Conversely, the same dose of intravenous ET-1 (25 pmol/kg) as that used in the intracerebroventricular experiment failed to cause any cardiovascular or renal sympathetic nerve responses. These results suggest that intracerebroventricular ET-1 acts in the central nervous system and causes a pressor response mainly through the enhancement of sympathoadrenal outflow.
High blood pressure due to alcohol. A rapidly reversible effect.
Authors: Maheswaran R , Gill J S , Davies P , Beevers D G
Published: June 2012

The hypothesis that the action of alcohol on blood pressure is rapidly reversible and that its effect is therefore mainly due to very recent alcohol consumption was examined in this study. Five hundred and seventy-seven subjects were screened in an occupational survey. Alcohol consumption, documented with a 1-week retrospective diary was divided into two categories: "recent" and "previous" intake. Recent intake was defined as the amount consumed on days 1, 2, and 3 immediately preceding blood pressure measurement. Previous intake was defined as the amount consumed on days 4, 5, and 6 preceding blood pressure measurement. High recent alcohol intake significantly raised systolic and diastolic blood pressure in both men and women. Previous alcohol intake, however, did not appear to influence blood pressure. We conclude that the effect of alcohol on blood pressure appears to be predominantly due to alcohol consumed in the few days immediately preceding blood pressure measurement, with alcohol consumption before those few days exerting little effect on blood pressure.
Sodium restriction in hypertensive patients treated with a converting enzyme inhibitor and a thiazide.
Authors: Singer D R , Markandu N D , Sugden A L , Miller M A , MacGregor G A
Published: June 2012

When the function of the renin system is inhibited, blood pressure becomes more dependent on changes in sodium and water balance. Diuretics alone and sodium restriction alone are additive to converting enzyme inhibitor therapy. However, it is not known if these two ways of reducing sodium balance are additive in the presence of established converting enzyme inhibition. We therefore performed a double-blind crossover study of the effects of moderate sodium restriction in 21 patients with essential hypertension who were already being treated with the combination of a converting enzyme inhibitor and a diuretic. After 1 month of captopril (50 mg twice daily) and hydrochlorothiazide (25 mg once daily) therapy, with their usual sodium intake, average supine blood pressure was 147/96 +/- 5/3 (SEM) mm Hg 2 hours after treatment. Patients then reduced their sodium intake to around 80-100 mmol/day for the remainder of the study. After 2 weeks of sodium restriction, they entered a double-blind, randomized, crossover study of Slow Sodium (100 mmol sodium/day) compared with Slow Sodium placebo, while continuing sodium restriction and the above treatment. During the double-blind study, after 1 month of treatment with captopril (50 mg twice daily), hydrochlorothiazide (25 mg once daily), and Slow Sodium placebo, supine blood pressure 2 hours after treatment was 138/88 +/- 4/2 mm Hg (24-hour urinary sodium 104 +/- 11 mmol). After 1 month of captopril (50 mg twice daily), hydrochlorothiazide (25 mg once daily), and Slow Sodium tablets, supine blood pressure 2 hours after treatment was 147/91 +/- 5/2 mm Hg (p less than 0.05; 24-hour urinary sodium 195 +/- 14 mmol).(ABSTRACT TRUNCATED AT 250 WORDS)
Augmentation of endothelium-independent flow constriction in pial arteries at high intravascular pressures.
Authors: Garcia-Roldan J L , Bevan J A
Published: June 2012

The effects of an increase in intraluminal pressure and flow on the diameter and active smooth muscle tone of pial arteries was studied in perfused segments. Resistance arteries (approximately 250-300 microns i.d.) were perfused under controlled pressure and flow conditions, and changes in arterial diameter registered with an automated video device. In any particular segment, diameter measurements were normalized to that observed at 5 mm Hg. Changes in active wall force were determined by relating the observed diameter under a particular set of conditions to the diameter at the same intramural pressure when smooth muscle tone was inhibited (calcium-free physiological saline solution) and to the diameter when smooth muscle cells were activated close to maximum (KCl; 89 mM). At 60 mm Hg, the diameter decrease of 21% in the absence of flow represented stretch-induced tone. No additional changes in diameter were encountered with a flow of 20 microliters/min. Diameter decreased a further 7% at 100 microliters/min. When intraluminal pressure was 90 mm Hg, diameter decreased 39% without flow. Additional constriction of 10% and 19% occurred at flows of 20 and 100 microliters/min, respectively. At the higher pressure, the vasoconstriction occasioned by flow was significantly greater than that at the lower pressure. After endothelium inactivation by passing hypo-osmotic Krebs' solution followed by air through the segment, mean diameter was less at each combination of pressure and flow, although this difference did not reach statistical significance. The diameter reductions to increases in pressure from 60 to 90 mm Hg and to flow at 40 microliters/min were not altered by endothelium inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Salt loads raise plasma fatty acids and lower insulin.
Authors: Goodfriend T L , Ball D L , Weinberger M H , Moore T J , Weder A B , Egan B M
Published: June 2012

Some fatty acids are potent inhibitors of angiotensin binding and aldosterone production in adrenal glomerulosa cells and thereby may be involved in regulating salt and water balance. To study the possible regulation of fatty acids by salt, we measured the levels of unesterified fatty acids in plasma from patients subjected to extremes of dietary salt intake and saline infusion. Insulin and catecholamines, two known regulators of plasma fatty acids, also were measured. Infusion of 2 l saline over 4 hours caused the levels of most unesterified fatty acids to rise. Total unesterified fatty acids rose 60-100%. A high salt diet caused a smaller rise in total unesterified fatty acids (approximately 33%). In both instances, oleic and palmitoleic acids showed the greatest proportionate increases, whereas stearic acid was relatively unaffected. When salt loads were administered by either intravenous or dietary routes, plasma insulin levels fell by approximately 50%. Plasma norepinephrine increased after saline infusion but not during a high salt diet. Postsaline levels of fatty acids correlated inversely with postsaline levels of aldosterone, supporting a possible role for fatty acids as physiological regulators of the adrenal glomerulosa. A rise in plasma fatty acids and fall in insulin in response to salt loads could act in concert to increase sodium excretion, constituting a physiological mechanism contributing to salt and water balance.
Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation.
Authors: Robertson D , Haile V , Perry S E , Robertson R M , Phillips J A , Biaggioni I
Published: June 2012

Dopamine beta-hydroxylase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.
Nitroprusside in preeclampsia. Circulatory distress and paradoxical bradycardia.
Authors: Wasserstrum N
Published: June 2012

In severe preeclampsia, short-term peripartum management of hypertension with hydralazine is complicated by relatively prolonged hypotensive episodes, resulting in fetal distress. We hypothesized that nitroprusside's rapid onset and brief antihypertensive action would permit more controlled blood pressure reduction. Nitroprusside was infused into 10 invasively monitored subjects until mean arterial pressure either 1) was gradually reduced 10-20% or 2) fell abruptly. Subjects fell into two groups, defined by whether the hypotensive effect of nitroprusside was accompanied by a fall in heart rate (group A, n = 8) or a rise (group B, n = 2). Group B showed the expected sinoaortic baroreceptor reflex elevations in heart rate (+17 +/- 6 beats/min) in response to moderate falls in mean arterial pressure (-32 +/- 9 mm Hg) elicited by moderate doses (1.03 +/- 0.23 micrograms/kg/min). However in group A, steep reductions in mean arterial pressure (-75 +/- 22 mm Hg, p less than 0.0001), significantly greater than in group B (p less than 0.05), occurred at much lower doses (0.35 +/- 0.23 micrograms/kg/min; p less than 0.05) and were accompanied by falls in heart rate (-21 +/- 7 beats/min). The apparently paradoxical falls in heart rate and extreme hypotensive responses in group A indicate severe circulatory compromise, corresponding to the cardiac and vasomotor depression that characterizes severe hemorrhage and other forms of acute/severe hypovolemic hypotension. This hemodynamic pattern represents a cardiopulmonary baroreceptor reflex presumably related to the Bezold-Jarisch reflex. The appearance of this pattern in the present study probably reflects the imposition of nitroprusside's prominent venous dilator action on the relatively reduced blood volume that generally characterizes severe preeclampsia.
Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition.
Authors: Clozel M , Kuhn H , Hefti F , Baumgartner H R
Published: June 2012

Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophage may lead to a better understanding of the mechanism of action of this class of drugs.
Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.
Authors: Pahor M , Bernabei R , Sgadari A , Gambassi G , Lo Giudice P , Pacifici L , Ramacci M T , Lagrasta C , Olivetti G , Carbonin P
Published: June 2012

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.
Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects.
Authors: Brickman A , Nyby M , von Hungen K , Eggena P , Tuck M
Published: June 2012

Relations between platelet cytosolic calcium, parathyroid hormone, and blood pressure were investigated in 91 normotensive subjects: 47 men and 44 women ranging in age from 24 to 70 years. The men had higher mean arterial blood pressure, serum creatinine, and body mass index than the women. Serum total calcium, plasma ionized calcium, and parathyroid hormone (measured as both intact hormone and mid-molecule fragment) were not different between men and women; however, serum phosphate was higher in women than in men. Basal platelet cytosolic calcium was higher in men than in women (113.7 +/- 1.9 versus 105.9 +/- 1.7, respectively; p less than 0.01), but there was no difference in the peak platelet cytosolic calcium responses to thrombin between the two groups. In the combined group of male and female subjects, platelet cytosolic calcium correlated with diastolic blood pressure and mean arterial pressure (r = 0.37, p less than 0.001 and r = 0.32, p less than 0.01, respectively). Intact parathyroid hormone correlated with systolic and mean arterial blood pressure (r = 0.41, p less than 0.001 for both). Age correlated with both systolic blood pressure (r = 0.40, p less than 0.001) and intact parathyroid hormone (r = 0.51, p less than 0.001). When multiple regression analysis was performed using mean arterial pressure as the dependent variable, platelet cytosolic calcium and intact parathyroid hormone maintained significant correlations with mean arterial pressure. Platelet cytosolic calcium did not correlate with intact parathyroid hormone. These results suggest that both platelet cytosolic calcium and intact parathyroid hormone are associated with blood pressure regulation in normotensive subjects. However, the influences of these two factors on blood pressure are not interrelated.