bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of spontaneous hypertension in rats by a vasopressin antagonist.
Authors: Sladek C D , Blair M L , Sterling C , Mangiapane M L
Published: June 2012

Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH2)5-Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V1) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CH2)5-D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension in SHR (p less than 0.05) without altering blood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 microgram/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p less than 0.007). Resting mean arterial pressure measured by indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 +/- 4 vs 157 +/- 4 mm Hg; p less than 0.05). Heart rate also was significantly reduced by the drug (351 +/- 6 vs 392 +/- 7 beats/min; p less than 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial hypertrophy in the fetal and neonatal spontaneously hypertensive rat.
Authors: Eccleston-Joyner C A , Gray S D
Published: June 2012

Large artery dimensions in prenatal and postnatal normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were evaluated to determine whether increased medial thickness is evident during early development. Microscopic cross-sections from perfusion-fixed aortas and carotid arteries of fetal (22-day gestation) and neonatal (5-day-old) animals were examined for numbers of laminae, luminal diameter and area, and medial thickness and area. SHR had a smaller mean body weight, and luminal diameters were the same in both strains. However, medial thickness and the numbers of laminae were significantly greater in SHR at both stages. Normalized ratios of medial thickness/luminal diameter and medial area/luminal area were also greater in SHR, indicating a disproportionate size of the arterial wall relative to the luminal space. Medial area/body weight ratios were also larger for SHR, suggesting the presence of greater medial mass per unit of body weight. The data support the view that the increased mass of the hypertensive arterial system is established in SHR as early as the fetal stage.
Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension.
Authors: Mayhan W G , Faraci F M , Heistad D D
Published: June 2012

The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
Failure of salt loading to inhibit tissue norepinephrine turnover in prehypertensive Dahl salt-sensitive rats.
Authors: Genain C P , Reddy S R , Ott C E , Van Loon G R , Kotchen T A
Published: June 2012

To determine if alterations of electrolyte balance or sympathetic nervous system activity are present in Dahl salt-sensitive rats (DS) before the onset of hypertension, we compared electrolyte balances, extracellular fluid volume (inulin space), plasma volume (radiolabeled albumin), and norepinephrine turnover in peripheral tissues (heart and interscapular brown fat) in prehypertensive DS and Dahl salt-resistant rats (DR). Animals were maintained for 5 to 7 days on either a "normal" or high NaCl diet. Tissue norepinephrine turnover was evaluated by measuring the rate at which norepinephrine content decreased following tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine. Blood pressure was higher (p less than 0.05) in DS (135 +/- 2 [SE] mm Hg) than in DR (129 +/- 2 mm Hg) and was not affected by the diets. Extracellular fluid volume and net Na+ and Cl- balances did not differ between DS and DR. However, plasma volume was greater in DS than in DR (p less than 0.05). In both fat and heart, norepinephrine turnover was decreased by dietary NaCl loading in DR (p less than 0.01), but not in DS. Thus, the tendency of the DS to become hypertensive with high NaCl intake may be related to the combined effects of an increased plasma volume and the failure of high dietary NaCl to inhibit peripheral sympathetic nervous system activity.
Systemic and regional hemodynamic effects of dietary calcium supplementation in mineralocorticoid hypertension.
Authors: DiPette D J , Greilich P E , Kerr N E , Graham G A , Holland O B
Published: June 2012

This study was undertaken to determine the systemic and regional hemodynamic effects of long-term dietary calcium supplementation in mineralocorticoid (DOC)-salt hypertension. Systemic and regional hemodynamic measurements were determined by the radioactive microsphere technique in conscious and unrestrained rats (kidneys intact) with DOC-salt-induced hypertension that were pair-fed either a normal calcium (0.6% by weight, n = 12) or a calcium-supplemented (high-calcium) diet (2.5% by weight, n = 12). After 7 to 8 weeks, there were no differences in weight, heart rate, or cardiac output between the two groups. In contrast, the high-calcium rats had a significantly lower mean blood pressure (125 +/- 4 mm Hg, mean +/- SEM) than the normal calcium rats (143 +/- 5 mm Hg); this finding appeared to result predominantly from a reduction in total peripheral resistance. The high-calcium rats had a higher renal blood flow (7.8 +/- 0.5% vs. 6.2 +/- 0.4% cardiac output; p less than 0.05) and lower renal (14.3 +/- 1 vs. 19.3 +/- 2 mm Hg/min/ml/g tissue; p less than 0.05) and jejunal vascular resistance than did the normal calcium rats. Two additional identical groups of normal calcium-and high-calcium-DOC-salt rats (n = 12 each) were also studied. In these rats, serum-ionized calcium decreased significantly (p less than 0.05) from baseline in both groups. Urinary sodium increased in both groups but did not differ significantly. In conclusion, dietary calcium supplementation attenuates the rise in peripheral vascular resistance that accompanies DOC-salt hypertension. This attenuated resistance appears to be relatively selective and is noted particularly in the renal vasculature.
Baroreceptor influences on oxytocin and vasopressin secretion.
Authors: Morris M , Alexander N
Published: June 2012

The objective of these studies was to investigate the role of arterial baroreceptors in the control of neurohypophyseal secretion. The effect of sinoaortic denervation on basal and osmotic-induced release of oxytocin and vasopressin and on blood pressure was determined. Hypertonic or isotonic saline was infused intravenously into sham-operated or denervated rats 3 days after surgery. Plasma oxytocin and vasopressin were measured at 5 and 15 minutes after the infusion. The control levels of oxytocin were increased in the denervated rats, but vasopressin levels were not significantly altered. The vasopressin and oxytocin responses to hypertonic saline were greater after baroreceptor denervation. Plasma oxytocin was increased from 4.7 +/- 0.9 to 72.2 +/- 8.7 pg/ml in the denervated rats and from 1.8 +/- 0.3 to 39.9 +/- 6.7 pg/ml in the sham-operated control group at 5 minutes after the infusion (p less than 0.01). The plasma vasopressin response to hypertonic saline was 7.1 +/- 0.6 pg/ml in the sham-operated versus 11.1 +/- 1.6 pg/ml in the denervated rats (p less than 0.05). There was no difference between sham-operated and denervated rats in the effect of hypertonic saline on plasma sodium and hematocrit. Mean arterial blood pressure was increased after sinoaortic denervation (116.3 +/- 4.2 mm Hg in the sham-operated vs. 138.2 +/- 8.3 mm Hg in the denervated rats, p less than 0.05); however, there was no difference in the pressor response to hypertonic saline. These results show that the baroreceptor system influences the secretion of both oxytocin and vasopressin, with effects on basal secretion as well as the response to an osmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamics and microcirculatory alterations in reduced renal mass hypertension.
Authors: Lombard J H , Hinojosa-Laborde C , Cowley A W
Published: June 2012

The objectives of this study were to determine the hemodynamic and microcirculatory changes that occur during reduced renal mass hypertension in rats. In conscious animals with 75% reduction of total renal mass, mean arterial pressure was initially (4-8 hours) elevated by 15-20 mm Hg during intravenous infusion with isonatremic (145.4 mM) NaCl. Cardiac index was elevated by 15-20%, and total peripheral resistance index was normal or reduced. Cardiac index subsequently returned toward normal, but mean arterial pressure remained elevated (20-40 mm Hg), presumably because of an elevated total peripheral resistance. Cremasteric arterioles were actively constricted (35-50%) in rats with short-term (36 hours), but not chronic (5-6 weeks) reduced renal mass hypertension. Total microvessel density was approximately 15% lower in maximally dilated cremaster muscles of chronically hypertensive rats versus sham-operated controls, which suggests that arterioles are lost during sustained reduced renal mass hypertension. Arteriolar constriction in response to increased superfusate PO2 (0% to 5% O2) was 2-4 times greater in rats with both short-term and chronic reduced renal mass hypertension than in normotensive controls, which suggests that oxygen-dependent autoregulatory mechanisms are altered. The hemodynamic and microcirculatory alterations observed in these experiments suggest that classic short-term autoregulatory mechanisms and an enhanced response of arterioles to increased oxygen availability contribute to the elevated total peripheral resistance in short-term reduced renal mass hypertension, whereas structural changes and altered vascular oxygen responses contribute to an elevated microvascular resistance in chronic reduced renal mass hypertension.
Prevalence of cardiac structural and functional abnormalities in untreated primary hypertension.
Authors: Laufer E , Jennings G L , Korner P I , Dewar E
Published: June 2012

We examined the prevalence of left ventricular structural and functional abnormalities in previously untreated subjects by performing echocardiography in 89 normal volunteers, 57 patients with established hypertension, and 38 patients with mild or borderline hypertension. We measured left ventricular mass, wall thickness, internal diameter, and wall thickness/radius ratio. Because of intergroup differences in body size, we used covariance analysis to index these variables to a common value of 1.8 m2. No adjustment was needed for the wall thickness/radius ratio. Functional variables determined were fractional shortening and transmitral early/late flow velocity ratio (the latter was standardized by analysis of covariance to age 40 years). The prevalence of left ventricular mass index values more than 2 SD above the mean of the normal group was 30% in the patients with established hypertension and 12-15% in the patients with mild hypertension. Corresponding figures for wall thickness index were 65% and 32% and for the wall thickness/radius ratio 60% and 40%. The prevalence of abnormality in the transmitral flow velocity was 28% in the patients with established hypertension and 12% in the patients with mild hypertension. A multivariate discriminant function that used combined anatomic and functional variables provided the most reliable classification; it was correct in 82% of normal subjects, 65% of patients with established hypertension, and 61% of patients with mild hypertension. The majority of patients with hypertension have cardiac structural or functional abnormalities, or both.
Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat.
Authors: Kurtz T W , Montano M , Chan L , Kabra P
Published: June 2012

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto ("WKY") rats are frequently employed in experimental studies of hypertension. Although both SHR and WKY rat strains have been presumed to be fully inbred, recent studies have revealed important biologic variability in WKY rats from different commercial sources. Genealogic evidence suggests that, in the United States, breeding stocks of WKY rats may have been distributed to major commercial suppliers as early as the F10 generation. To test the hypothesis that commercially available WKY rats are genetically heterogeneous, we performed deoxyribonucleic acid (DNA) "fingerprint" analysis on genomic DNA of WKY rats from two of the largest vendors in the United States, Taconic Farms and Charles River Laboratories. We found molecular evidence of genetic variability not only among WKY rats from two different breeding facilities, but also among WKY rats within a single breeding facility (Taconic Farms). Although some studies have suggested the possibility of biologic variability in SHR from different sources, preliminary studies have not revealed molecular evidence of genetic heterogeneity in SHR from these vendors. In demonstrating genetic variability in WKY rats from different sources, the current study provides compelling evidence that rats designated WKY do not constitute an inbred strain. Accordingly, the results of studies in which SHR and WKY rats are compared might vary because of genetic heterogeneity in "the WKY rat control strain."
Endothelium-mediated spontaneous response in aortic rings of deoxycorticosterone acetate-hypertensive rats.
Authors: Rinaldi G , Bohr D
Published: June 2012

Aortic rings isolated from normotensive Sprague-Dawley rats (CONT) exhibited spontaneous tone when the preparations were stretched. After administering deoxycorticosterone acetate (DOCA), the rats became hypertensive, and this spontaneous tone increased remarkably. The spontaneous tone was dependent on the extracellular calcium concentration. Incubation with the calcium entry blocker D-600 attenuated the spontaneous response to a greater degree in rings from DOCA rats than in rings from CONT rats. Nifedipine relaxed the already developed spontaneous tone. Removal of the endothelium greatly depressed spontaneous tone, but did not diminish the contraction caused by norepinephrine. On the basis of our findings, we conclude that 1) spontaneous tone depends on calcium influx, presumably through specific stretch-operated membrane channels, 2) these stretch-dependent channels are blocked by D-600 and nifedipine, 3) spontaneous tone is enhanced in DOCA hypertension, and 4) the endothelium appears to act as a receptor for stretch, mediating--at least in part--the spontaneous contractile response by releasing a constrictor agent.
Effects of chronic infusion of renin inhibitor A-64662 in sodium-depleted monkeys.
Authors: Verburg K M , Kleinert H D , Kadam J R , Chekal M A , Mento P F , Wilkes B M
Published: June 2012

The potent and primate-selective renin inhibitor A-64662 (n = 8) or vehicle (n = 6) was administered intravenously for 7 days to sodium-depleted cynomolgus monkeys to investigate the chronic effects on arterial pressure, sodium excretion, and the renin-angiotensin-aldosterone system. A 0.1-mg/kg i.v. bolus followed by a continuous 0.01-mg/kg/min infusion of A-64662 lowered mean arterial pressure from 89 +/- 3 (average of 4 control days) to 75 +/- 4 mm Hg (p less than 0.05) after 1 day of administration. This decrement was associated with marked inhibition of plasma renin activity (PRA) from 57.7 +/- 11.1 to 1.3 +/- 0.6 ng angiotensin I (Ang I)/ml/hr (p less than 0.05). Similar hypotensive levels (range 73 +/- 4 to 77 +/- 4 mm Hg) were observed on days 2-7 of A-64662 infusion and PRA remained suppressed, ranging from 0.6 +/- 0.4 to 1.9 +/- 1.0 ng Ang I/ml/hr. Plasma angiotensin II (Ang II) levels were reduced (p less than 0.05) from the control value of 66.7 +/- 20.2 to 12.4 +/- 3.3 and 26.4 +/- 6.5 pg/ml on the second and seventh days, respectively, of A-64662 infusion. In contrast, infusion of vehicle alone had no discernible effect on mean arterial pressure, PRA, or plasma Ang II concentrations. Plasma aldosterone decreased (p less than 0.05) from control on the second and third days of A-64662 infusion, although differences between the treatment groups were not detected throughout the study. Urinary sodium excretion remained at control levels throughout the infusion of A-64662. Cessation of A-64662 administration resulted in a recovery of mean arterial pressure to preinfusion levels within 1 day. This study indicates that continuous infusion of A-64662 results in a sustained hypotension in sodium-depleted monkeys. This effect appears to be related, at least partially, to inhibition of PRA and lower plasma Ang II levels.
Sodium-lithium countertransport and blood pressure: the Gubbio Population Study.
Authors: Laurenzi M , Trevisan M
Published: June 2012

The relation of red blood cell sodium-stimulated lithium countertransport to blood pressure (BP) and prevalence of hypertension was assessed in univariate and multivariate analyses for 2,748 men and women aged 25-74 years who participated in the baseline examination of the Gubbio Population Study in north central Italy. Since age-specific countertransport values were consistently higher for men than women, all analyses were done for men and women separately. In simple correlation analyses, countertransport was significantly related to systolic and diastolic BP in both sexes (r values 0.107-0.163). In age-adjusted analyses, countertransport was significantly related to BP level of both men and women not receiving antihypertensive treatment; mean levels were high for hypertensive persons receiving antihypertensive therapy compared with normotensive persons. Age-adjusted prevalence rates of hypertension were progressively higher for both sexes in successively higher quintiles of countertransport, almost twice as high for those in the highest quintile compared with those in the lowest quintile. Correspondingly, age-adjusted logistic regression analyses showed countertransport to be related significantly to prevalence of hypertension for both men and women (p less than 0.001). Since age, body mass index, plasma total cholesterol, uric acid, glucose, urinary sodium/potassium excretion, pulse, and (for men) daily alcohol intake also were significantly correlated with BP, and in some instances with countertransport, relation of countertransport to BP was also assessed in multivariate analyses with control for these variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Ploidy in mesenteric vessels of aged spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Lombardi D M , Owens G K , Schwartz S M
Published: June 2012

Long-term regulation of blood pressure in a hypertensive rat may be mediated by elevated DNA content of smooth muscle cells of resistance vessels. This study explores DNA changes represented by an increased frequency of polyploid cells in multiple levels of the mesenteric arterial tree of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats. Two ages were examined: 45 and 78-80 weeks of age. SHR and WKY rats did not differ in frequency of polyploid cells at any mesenteric branch level at either age. Although hypertension per se seemed not to be a factor, both species showed increased numbers of polyploid cells with aging at certain branch levels of the mesenteric arterial tree. The data in the current study support the idea that hypertension and aging may result in similar and possibly additive changes in DNA in the vessel wall.
Effects of perfusion pressure on energy and work of isolated rat hearts.
Authors: Watters T , Wikman-Coffelt J , Wu S , James T L , Sievers R , Parmley W W
Published: June 2012

A chemomechanical study of hypertrophied hearts of 6-month-old spontaneously hypertensive rats (SHR) and that of age-matched Wistar-Kyoto (WKY) rats was carried out, analyzing the response of the heart to steady-state changes in coronary perfusion pressure. The ratio of heart (dry)-to-body (wet) weight of WKY rats was 0.37 +/- 0.02 (10(-3] and for SHR was 0.58 +/- 0.03 (10(-3] (p less than 0.01). In the apex-ejecting, isolated, pyruvate-perfused working hearts of WKY rats and SHR, coronary flow was constant when coronary perfusion pressure was set between 140 and 190 cm H2O (range of autoregulation). Coronary flow was perfusion pressure dependent when the coronary perfusion pressure was set below 110 cm H2O for both WKY rats and SHR. Cardiac output, developed pressure, rate of pressure development (dP/dt), and oxygen consumption were constant in the range of autoregulation but decreased in the direction of coronary flow when coronary flow was reduced by a drop in perfusion pressure. Similarly, the phosphorylation potential, phosphocreatine, adenosine triphosphate, and cyclic adenosine monophosphate were constant in the range of autoregulation but decreased directionally with coronary perfusion pressure below 110 cm H2O for both SHR and WKY rats. There was a significantly lower phosphorylation potential in SHR as compared with WKY rats when coronary perfusion pressure was reduced to 80 cm H2O. In the region of autoregulation, coronary flow and oxygen consumption were significantly less in SHR, although developed pressure was significantly greater at both high and low workloads.(ABSTRACT TRUNCATED AT 250 WORDS)
Dissociation of renal nerve and excretory responses to volume expansion in prehypertensive Dahl salt-sensitive and Dahl salt-resistant rats.
Authors: Veelken R , Sawin L L , DiBona G F
Published: June 2012

Prehypertensive Dahl salt-sensitive rats on low sodium diet have impaired baroreceptor and cardiopulmonary receptor function as compared with Dahl salt-resistant control rats. We tested whether these abnormalities influenced the ability of conscious prehypertensive Dahl salt-sensitive rats to excrete a moderate intravenous isotonic saline volume load (0.9% NaCl, 3% body weight i.v.). During control, 30-minute volume expansion, and 2-hour recovery periods, arterial blood pressure and heart rate did not change. Glomerular filtration rate and renal plasma flow remained stable throughout control and recovery. The amount of the volume load excreted as either water or sodium was the same for Dahl salt-sensitive and Dahl salt-resistant rats with either denervated or innervated kidneys. The time course of water and sodium excretion was similar in Dahl salt-sensitive and Dahl salt-resistant rats. Renal sympathetic nerve activity, however, showed different patterns. Although the initial decrease in renal sympathetic nerve activity during volume expansion was similar for both groups, Dahl salt-sensitive rats exhibited a prompt return of renal sympathetic nerve activity to control levels, whereas renal sympathetic nerve activity in Dahl salt-resistant rats remained decreased throughout the recovery period. The rapid recovery of renal sympathetic nerve activity to control levels after volume expansion in Dahl salt-sensitive rats supports the concept of impaired cardiopulmonary receptor function in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of kidney dopamine in the natriuretic response to volume expansion in rats.
Authors: Hegde S S , Jadhav A L , Lokhandwala M F
Published: June 2012

It has been postulated that endogenously produced dopamine (DA) may play a role in the regulation of renal sodium excretion. In the present study, experiments were designed to test the hypothesis that acute volume expansion with isotonic sodium chloride stimulates the production of DA within the kidney, which in turn acts on specific DA1 receptors to promote sodium excretion. In pentobarbital-anesthetized rats, acute volume expansion over a period of 1 hour evoked a pronounced increase in urine output and urinary sodium excretion. These diuretic and natriuretic effects were not accompanied by any significant changes in blood pressure or heart rate. However, there was a significant elevation in central venous pressure and a transient rise in glomerular filtration rate. The natriuretic and diuretic response was accompanied by a significant increase in urinary DA excretion, and this effect was clearly dissociated from the rise in glomerular filtration rate. In a separate group of rats, the effects of acute volume expansion were studied in the presence of selective DA1 receptor antagonist SCH-23390 (50 micrograms/kg i.v. bolus; 10 micrograms/kg/min). During DA1 receptor blockade, there was a marked attenuation in the diuretic and natriuretic response throughout the period of volume expansion, when compared with that in the control group. The changes in central venous pressure and glomerular filtration rate were identical in the two groups. In another group of rats, the renal effects of exogenously administered DA were studied. DA (0.5 micrograms/kg/min) produced significant increases in urine output and urinary sodium excretion, without causing any alterations in blood pressure or glomerular filtration rate, suggesting a tubular site of action.(ABSTRACT TRUNCATED AT 250 WORDS)
Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat.
Authors: Auch-Schwelk W , Katusic Z S , Vanhoutte P M
Published: June 2012

To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endothelium-dependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygen-derived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals.
Evidence for heritability of non-modulating essential hypertension.
Authors: Lifton R P , Hopkins P N , Williams R R , Hollenberg N K , Williams G H , Dluhy R G
Published: June 2012

We have previously described a subset of subjects with essential hypertension who fail to appropriately modulate renal vascular and adrenal reactivity with changes in dietary sodium and in response to infused angiotensin II (Ang II). In this paper, we studied these responses in 13 unselected hypertensive subjects in whom the family history of hypertension had been carefully detailed. Nine of these 13 subjects had a positive family history (FH+) for hypertension and had significantly smaller decrements in renal blood flow with Ang II infusion than the four subjects who had a negative family history (FH-) (-84 +/- 16 ml/min/1.73 m2 for FH+ vs. -149 ml/min/1.73 m2 for FH-, p = 0.024). These FH+ subjects also showed smaller increases in renal blood flow with increases in dietary sodium than FH- subjects (7 +/- 10 ml/min/1.73 m2 vs. 72 +/- 24 ml/min/1.73 m2, respectively; p = 0.014). When classified as modulators or non-modulators by previously established criteria, all seven non-modulators were FH+, and seven of nine FH+ subjects were non-modulators. This association between non-modulation and family history of hypertension is significant (p = 0.021). To further clarify the association between non-modulation and family history of hypertension, we have studied the renal blood flow response to Ang II in 31 hypertensive siblings from 14 sibships. Twenty-five of these 31 subjects (81%) behaved as non-modulators (p = 0.008 compared with expected value in an unselected hypertensive population). Additionally, strong concordance of non-modulation between sibling pairs was observed (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
Increased sodium-calcium exchange in arterial smooth muscle of spontaneously hypertensive rats.
Authors: Ashida T , Kuramochi M , Omae T
Published: June 2012

We compared sodium-calcium (Na-Ca) exchange in vascular smooth muscle between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Aortic rings of 11 SHR and 11 WKY rats aged 11-12 weeks were superfused with physiological saline, and isometric tension was measured. Systolic blood pressure was higher in SHR (174 +/- 12 mm Hg) than in WKY rats (132 +/- 4 mm Hg): 1) In the presence of 10 microM phentolamine, 10 microM verapamil, and 5 mM caffeine, reduction of ionized extracellular sodium concentration [( Na+]o) from normal (139.2 mM) to 1.2 mM (replaced by N-methyl-D-glucamine) caused an external Ca2+-dependent increase in tonic tension (calcium entry by Na-Ca exchange). The rate of increase was higher in SHR (35.4 +/- 3.9 mg/min) than in WKY rats (17.9 +/- 1.3 mg/min) (p less than 0.01). 2) In the presence of phentolamine, verapamil, and caffeine, relaxation from low-Na+ contraction was promoted by external calcium removal. The rate of relaxation was directly related to [Na+]o. The rates of relaxation at normal (139.2 mM) [Na+]o were higher in SHR than in WKY rats (p less than 0.05). The rates of relaxation at 1.2 mM [Na+]o (calcium extrusion by adenosine triphosphate-driven calcium pump) were not different between SHR (11.6 +/- 2.8 mg/min) and WKY rats (8.9 +/- 2.5 mg/min). The increase in the rates of relaxation from 1.2 mM to normal (139.2 mM) [Na+]o (calcium extrusion by Na-Ca exchange) was greater in SHR (34.9 +/- 6.6 mg/min) than in WKY rats (17.1 +/- 4.5 mg/min) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin in neuronal cultures from neonatal rat brain.
Authors: Cheng S W , Wilson K M , Mulchahey J J , Stallworth J W , Berecek K H
Published: June 2012

This study was performed to characterize and quantify vasopressin in neuron-enriched primary cultures of whole brains from 1-day-old rats and to compare such cultures between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Vasopressin was extracted from cells and evaluated by radioimmunoassay and high-pressure liquid chromatography. Radioimmunoassay of high-pressure liquid chromatography fractions from cell extracts showed that the major peak of immunoreactivity comigrated with synthetic vasopressin. Cell vasopressin content increased in a graded manner when one to six dishes (plated 8 x 10(6) cells/dish) were pooled (8.7 +/- 0.5 to 67.7 +/- 8.2 pg/dish). When the number of plated cells per dish was increased (2 to 16 x 10(6) cells), there was also a graded rise in dish vasopressin content (3.4 +/- 0.4 to 15.3 +/- 3.9 pg). Treatment of cultures with 100 aM to 1 nM of angiotensin II for 5 minutes caused a dose-dependent decrease in cell vasopressin content. Furthermore, the decrease in cell vasopressin content of cultures treated with 1 nM angiotensin II (12.6 +/- 0.8 to 7.0 +/- 1.0 pg/10(6) cells, p less than 0.05) corresponded with the increase in medium vasopressin concentration (3.8 +/- 0.5 to 7.5 +/- 2.3 pg/ml) and this vasopressin-releasing effect of angiotensin II was blocked by [Sar1, Thr8]angiotensin II. Treatment of cultures with potassium chloride (56 mM) and acetylcholine chloride (5.5 microM) also resulted in significant decreases in cell vasopressin content.(ABSTRACT TRUNCATED AT 250 WORDS)
Aggravation of salt-induced hypertension in Dahl rats by 2% supplemental dietary calcium.
Authors: Peuler J D , Mark A L
Published: June 2012

There is considerable interest in the antihypertensive potential of supplemental dietary calcium in salt-sensitive hypertension. Previously we reported that very high dietary calcium (4.0% vs. 0.4%) lowers mean arterial pressure in Dahl salt-sensitive (DS) hypertensive rats. However, we have recently observed that more moderate calcium supplementation (2.0% vs. 0.4%) increases mean arterial pressure in DS rats. To further evaluate the pressor action of 2.0% versus 0.4% calcium, we tested for effects of 2.0% calcium in female DS rats fed low (0.2%), moderate (1.0%), and high (2.7%) sodium and in Dahl salt-resistant (DR) rats fed high sodium from 6 to 12 weeks old (n = 10-13 rats per group). At 12 weeks, 2.0% calcium increased mean arterial pressure and the cardiac ventricular weight/body weight ratio in DS rats fed high sodium (p less than 0.05) but not in DS rats fed low or moderate sodium or in DR rats fed high sodium. Ganglionic blockade decreased mean arterial pressure in all groups but failed to abolish or attenuate the difference in mean arterial pressure between high sodium-fed DS rats on 2.0% and 0.4% calcium diets. In the same DS rats fed a high sodium diet, 2.0% calcium increased systemic pressor responsiveness to graded norepinephrine administration after ganglionic blockade. Thus, 2.0% supplemental calcium intake enhances salt-induced hypertension in DS rats. This prohypertensive action of 2.0% calcium is dependent on a critically high level of between 1.0% and 2.7% sodium in the diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension.
Authors: Kelly R , Daley J , Avolio A , O'Rourke M
Published: June 2012

We compared dilevalol (an isomer of labetalol), 200-400 mg daily, against atenolol, 50-100 mg daily, in a double-blind, crossover, placebo-controlled trial with respect to effects on arterial distensibility (measured as pulse wave velocity [PWV]) and wave reflection (assessed from carotid pressure wave contour). Twelve patients of mean age 58 years (range 44-73 years) with essential hypertension (supine diastolic blood pressure 95-114 mm Hg) took active therapy for 12 weeks, separated by a 2-4 week placebo period. Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. PWV was measured between carotid and femoral arteries (aortic PWV), carotid and radial arteries (arm PWV), and femoral and pedal arteries (leg PWV). Early wave reflection was calculated from the ratio of the height of the peak of the carotid wave above its shoulder to the pulse pressure and was expressed as an augmentation index. Both drugs were equally effective in reducing brachial sphygmomanometric pressure and PWV in all three regions (active vs. placebo, p less than 0.001), but there was no significant difference between the two active therapies. However, the augmentation index (averaged during the treatment period) was significantly lower with dilevalol (19%) than with atenolol (28%, p less than 0.01), corresponding to a greater decrease of 5-8 mm Hg in carotid systolic pressure compared with the brachial artery. Although both drugs were equally effective in reducing arterial distensibility, the vasodilating action of dilevalol gave added benefit in reducing wave reflection, presumably through its vasodilatory effect on peripheral conduit arteries.
Seasonal influences on blood pressure in high normal to mild hypertensive range.
Authors: Giaconi S , Ghione S , Palombo C , Genovesi-Ebert A , Marabotti C , Fommei E , Donato L
Published: June 2012

To investigate the seasonal influences on various arterial blood pressure measurements, 22 subjects in the high normal to mild hypertensive range were examined twice following the same protocol. In one group (13 subjects), measurements were first done in warm conditions and repeated 5-7 months later in cold conditions; in the second group (nine subjects) a reverse sequence was followed. Blood pressure was measured under casual conditions during a hand grip exercise test, mental arithmetic test, and submaximal multistage bicycle exercise test; during the following 24 hours, blood pressure was measured serially with a noninvasive ambulatory blood pressure recorder. Daily outdoor maximum and indoor laboratory temperatures were also obtained. In the cold season, significantly higher values (on the average by 5-10 mm Hg, p less than 0.01) were obtained in both groups for mean diastolic daytime blood pressure. For other measurements, a trend toward higher values in the cold season was observed in both groups, although statistical significance was not obtained in all instances. For nighttime measurements, irrespective of the seasonal sequence, lower values were observed in the second session. Significant correlations were found between the differences in the average daytime ambulatory blood pressures and the corresponding changes of daily maximum outdoor temperatures after 5-7 months. These observations indicate that arterial blood pressure may be strongly influenced by environmental temperature. This phenomenon should be taken into account both in the evaluation of the individual hypertensive patients and in the design and analysis of studies on arterial hypertension, especially when ambulatory blood pressure techniques are employed.
Body fluid volume and angiotensin II in maintenance of one-kidney, one clip hypertension.
Authors: Akahoshi M , Carretero O A
Published: June 2012

To investigate the possible role of body fluid volume or the renin-angiotensin system in the maintenance of high blood pressure in chronic one-kidney, one clip (1K1C) hypertension, we studied whether blood pressure remained high after removal of the clip while the body fluid volume was kept constant or when angiotensin II (Ang II) was infused in conscious 1K1C rats. Blood pressure fell 58 +/- 13 mm Hg in 1K1C rats after removal of the clip. When body fluid volume was kept at the same level as before "unclipping," blood pressure fell only 9 +/- 2 mm Hg after removal of the clip; if body fluid volume was then allowed to decrease, blood pressure fell an additional 55 +/- 8 mm Hg. When Ang II was infused after removal of the clip, blood pressure fell 26 +/- 7 mm Hg despite the fact that plasma Ang II increased to nonphysiological concentrations (1,161 +/- 353 pg/ml). After Ang II infusion was stopped, blood pressure fell an additional 44 +/- 13 mm Hg. When Ang II was infused and body fluid volume kept constant, blood pressure still did not change after removal of the clip, although plasma Ang II concentrations increased to nonphysiological levels (618 +/- 98 pg/ml). After the Ang II infusion was discontinued and the body fluid volume was no longer kept constant, blood pressure fell 78 +/- 9 mm Hg. These data further support the hypothesis that a volume factor, not the renin-angiotensin system, is important in the maintenance of high blood pressure in 1K1C hypertension.
Atrial natriuretic factor in NaCl-sensitive and NaCl-resistant spontaneously hypertensive rats.
Authors: Jin H , Chen Y F , Yang R H , Oparil S
Published: June 2012

Our previous studies demonstrated that chronic dietary NaCl supplementation is associated with significant increases in plasma atrial natriuretic factor in Wistar-Kyoto (WKY) rats but not in NaCl-sensitive spontaneously hypertensive rats (SHR-S). The current study tested the hypotheses that 1) acute volume-induced atrial natriuretic factor release is impaired in SHR-S compared with control NaCl-resistant SHR (SHR-R) and WKY rats maintained on basal (1%) NaCl diets; 2) dietary NaCl supplementation (8% NaCl for 2 weeks) alters acute volume-dependent atrial natriuretic factor release in these strains; and 3) replacement of the deficiency in circulating atrial natriuretic factor seen in NaCl-supplemented SHR-S can reverse the NaCl-sensitive component of hypertension. SHR-S and control SHR-R and WKY rats were placed on 1% or 8% NaCl diets at age 7 weeks; 2 weeks later, right atrial pressure and plasma atrial natriuretic factor were measured in conscious rats before and after acute volume expansion (7, 20, and 60 ml/kg, 5% dextrose, for 1 minute). The slopes of the right atrial pressure x plasma atrial natriuretic factor linear regression for the SHR-S fed both 1% and 8% NaCl were significantly shallower (p less than 0.01) than those of 1% NaCl-fed SHR-R or WKY rats. Dietary NaCl supplementation did not alter right atrial pressure in any strain and blunted acute volume-induced atrial natriuretic factor release in WKY rats, but not in SHR-S or SHR-R, suggesting the dietary NaCl-induced elevation in plasma atrial natriuretic factor levels in WKY rats may be related to impaired clearance, as well as enhanced release, of the peptide. The plasma levels of exogenous atrial natriuretic factor required to abolish the NaCl-induced pressor effect in SHR-S were 12-fold greater than endogenous plasma atrial natriuretic factor levels in 8% NaCl-fed WKY rats, suggesting that impairment of atrial natriuretic factor release does not play a major role in the pathogenesis of NaCl-sensitive hypertension in SHR-S.
Effects of renin inhibition in the conscious primate Macaca fascicularis.
Authors: Hui K Y , Knight D R , Nussberger J , Hartley L H , Vatner S F , Haber E
Published: June 2012

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a monoclonal antibody to angiotensin II on hemodynamic responses to noradrenergic stimulation in pithed rats.
Authors: Wong P C , Reilly T M , Timmermans P B
Published: June 2012

A specific angiotensin II monoclonal antibody, KAA8, was used to examine the interaction between sympathetic function and angiotensin II in pithed rats. KAA8, at 5 or 50 mg/kg i.v., did not alter the mean blood pressure, cardiac output, total peripheral resistance, or heart rate responses to sympathetic neural stimulation (0.25-4.0 Hz) or to norepinephrine (0.3-3 micrograms/kg i.v.) but blocked significantly the hemodynamic responses to angiotensin II (0.03-1.0 microgram/kg i.v.) and to angiotensin III (0.3-10 micrograms/kg i.v.). KAA8 treatment also reduced the plasma immunoreactive angiotensin II from 2,880 +/- 475 pg/ml to an undetectable level. In contrast, captopril (5 mg/kg i.v.) and saralasin (10 or 50 micrograms/kg/min i.v.) inhibited the mean blood pressure and total peripheral resistance responses, but not the cardiac output and heart rate responses, to sympathetic neural stimulation and to norepinephrine. These results, which confirm previous findings by Kaufman and Vollmer (Kaufman LJ, Vollmer RR: Endogenous angiotensin II facilitates sympathetically mediated hemodynamic responses in pithed rats. J Pharmacol Exp Ther 1985;235:128-134), demonstrate that angiotensin II selectively potentiates the sympathetic vascular function in the pithed rat. However, our results suggest that circulating angiotensin II does not appear to interact with the sympathetic vascular function. It is speculated that in the pithed rat the sympathetic vascular response is enhanced by vascular-formed angiotensin II.