bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased neural atrial natriuretic factor generation in spontaneously hypertensive rats.
Authors: Debinski W K , Kuchel O G , Thibault G
Published: June 2012

The increased neural atrial natriuretic factor (ANF) concentrations in spontaneously hypertensive rats compared with Wistar-Kyoto control rats prompted us to examine the basis of this phenomenon. Central and peripheral neural tissues from both strains were processed under rigorous antiproteolytic conditions, which were monitored by degradation of purified and iodo-labeled proANF or synthetic ANF[Ser99, Tyr126]. The extracted material was separated on a reverse-phase high-pressure liquid chromatography system, and eluates were determined for immunoreactive ANF with radioimmunoassays, employing antibodies directed against two different fragments of the ANF prohormone. The chromatographic pattern of immunoreactive-ANF elution showed the clear presence of proANF in all neural tissues studied. This pattern also included an intermediate ANF and COOH-terminal of proANF whose relative varying content was tissue dependent. Superior cervical ganglia contained most of the immunoreactive ANF corresponding to proANF and intermediate ANF. Total immunoreactive ANF in the hypothalamus, brainstem, and upper and lower parts of the spinal cord was always higher in spontaneously hypertensive than in Wistar-Kyoto rats. However, there was no difference in the content of the main molecular forms of ANF in any of their neural tissues. We suggest that the increase in neural ANF in spontaneously hypertensive rats does not arise from posttranslational alterations and may indicate an enhanced ANF synthesis rate or accumulation, or both.
Effect of 8-bromo-cyclic guanosine monophosphate on intracellular pH and calcium in vascular smooth muscle.
Authors: Lockette W , McCurdy R , Aronow H , Butler B
Published: June 2012

Endothelium-dependent vasodilators, nitrates, and atrial natriuretic factor relax blood vessels by increasing vascular cyclic guanosine monophosphate (cGMP). The mechanisms by which cGMP relaxes vascular smooth muscle (VSM) are not known. Since contraction of VSM is associated with increased intracellular calcium and pH, we hypothesized that cGMP may decrease vascular tone by lowering ionized, intracellular calcium [( Ca2+]i) and pH. We used microfluorometry to measure cGMP-induced changes in intracellular calcium and pH of cultured A7r5 VSM cells after stimulation with contractile agonists. A cGMP analogue, 8-Br-cGMP, blocked vasopressin- but not thrombin-stimulated increases in [Ca2+]i. High extracellular potassium concentrations [( K+]) increased [Ca2+]i, but the attenuation of [Ca2+]i by 8-Br-cGMP was not statistically significant. 8-Br-cGMP also attenuated vasopressin- but not thrombin-stimulated alkalinization of VSM cells. cGMP may decrease vascular tone by decreasing [Ca2+]i and pH, but these changes are dependent on the contractile agonist studied.
Alcohol suppresses endothelium-dependent relaxation in rat mesenteric vascular beds.
Authors: Criscione L , Powell J R , Burdet R , Engesser S , Schlager F , Schoepfer A
Published: June 2012

The effects of prolonged infusions of ethanol on endothelium-dependent vasorelaxation induced by acetylcholine and adenosine triphosphate (ATP) and on endothelium-independent relaxation induced by papaverine were studied and compared in isolated perfused rat mesenteric artery preparations. Infusion of ethanol over 60 minutes at concentrations of 1.6, 4.7, 6.3, and 7.9 mg/ml caused concentration-related inhibition of norepinephrine-induced vasoconstriction. In preparations infused with 6.3 and 7.9 mg/ml, this effect reached a maximum after 10-20 minutes but had vanished by the end of the infusion; 1 hour after the end of the infusion, the effects of norepinephrine were potentiated by 71% and 108%, respectively. Acetylcholine-induced vasorelaxation (EC50 3.0 ng/ml in controls) was significantly reduced after 6.3 mg/ml ethanol infusion and totally abolished after 7.9 mg/ml ethanol infusion. ATP-induced vasorelaxation (EC50 180 ng/ml in controls) was also abolished after 7.9 mg/ml of ethanol infusion. By contrast, the vasorelaxant effects of papaverine were not affected by 7.9 mg/ml ethanol infusion. Light-microscopic examination revealed that the endothelial cells were present in ethanol-treated and in control mesenteric arterial beds. These observations indicate that ethanol suppresses endothelium-dependent vasorelaxation without apparent removal of the endothelial cells. The compromised relaxant capacity of the endothelium after ethanol and the resultant intensification of the vasoconstrictor response to norepinephrine may contribute to the development of vascular diseases such as hypertension and stroke.
Enhanced release of atrial natriuretic factor by endothelin in atria from hypertensive rats.
Authors: Winquist R J , Scott A L , Vlasuk G P
Published: June 2012

Intravenous (bolus) administration of endothelin results in a transient fall in blood pressure that is accentuated in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto normotensive rats (WKY). In attempting to discern possible mechanisms underlying this depressor response, we examined the ability of endothelin to release atrial natriuretic factor (ANF) from isolated, spontaneously contracting atria from SHR and WKY. Isolated right atria were suspended under 3.0 g of resting force in tissue baths with the amount of immunoreactive ANF (irANF) released after exposure to endothelin assessed by radioimmunoassay. Endothelin (10(-8) and 10(-7) M) caused a concentration-dependent increase (1.5-4.5-fold) in the release of irANF, which was significantly greater in atria of SHR compared with WKY. The greater release of irANF in atria of SHR versus WKY was not related to tissue weight or changes in contractile rate or force induced by endothelin. Therefore, endothelin appears to cause a direct release of irANF from rat right atria in vitro. As found for the depressor response in vivo, endothelin is more efficacious in the hypertensive compared with the normotensive atrial preparation. Release of ANF may be important in the hypotensive response to endothelin in vivo.
Arteriolar changes in developing and chronic stages of two-kidney, one clip hypertension.
Authors: Ono Z , Prewitt R L , Stacy D L
Published: June 2012

Arteriolar internal and external diameters in the cremaster muscle of two-kidney, one clip hypertensive rats (2K1C) were measured in vivo with video microscopy, both before and after the topical application of adenosine (10(-4) M). Arteriolar density was determined by stereologic techniques. Mean arterial blood pressure was significantly elevated in the 2K1C rats, rising to 186 +/- 6 mm Hg by 8 weeks compared with 113 +/- 4 mm Hg in controls. Lumens of larger arterioles showed a structural reduction at 2 weeks of hypertension and remained at the same level through 8 weeks, while arterioles of control rats showed a progressive increase in diameter with age (101 +/- 6 microns in 2K1C vs. 158 +/- 8 microns in controls at 8 weeks after operation). Wall-to-lumen ratios of larger arterioles were significantly increased at 2, 4, and 8 weeks of hypertension, but cross-sectional wall area was significantly reduced at 8 weeks. Medial hypertrophy was not evident at any stage of hypertension. Arteriolar rarefaction of smaller arterioles was functional at 2 weeks and structural at 8 weeks of hypertension. Vascular tone of the smaller arterioles was elevated in the developing and chronic stages of hypertension. At 2 weeks of hypertension when the structural reduction in diameters of larger arterioles was progressing, the increased vasoconstriction and functional rarefaction may have contributed to the elevated resistance. At 8 weeks, the marked diameter reductions of larger arterioles (36% in first-order arterioles and 25% in second-order arterioles) account for most of the increased resistance to flow.
Renal vasomotion in essential hypertension: influence of vasodilators.
Authors: Hollenberg N K , Sandor T , Holtzman E , Meyerovitz M F , Harrington D P
Published: June 2012

To assess factors responsible for phasic behavior of renal blood flow in essential hypertension, we applied an analytic method based on the estimation of power spectral density to xenon transit through the kidney and examined the renal vasodilator response to a range of agents in 53 normal subjects and 53 patients with essential hypertension. The renal vasodilator response to the calcium channel blocking agent diltiazem, but not the response to alpha-adrenergic blockade (phentolamine) or angiotensin converting enzyme inhibition (teprotide or captopril), was associated with a significant reduction in the amplitude of renal vasomotion. Acetylcholine, a vasodilator that acts through the release of a vasorelaxant factor or factors from endothelium, induced an unanticipated increase in renal vasomotion. These observations further dissociate factors responsible for basal renal vascular tone and periodic changes in renal vascular tone and raise the possibility that abnormalities in the flux of calcium into renal arterioles contribute to increased renal vasomotion in essential hypertension.
Calcium infusion increases plasma atrial natriuretic factor in spontaneously hypertensive rats.
Authors: Fujimura A , Lowry R W , Kem D C
Published: June 2012

The effect of calcium on plasma atrial natriuretic factor (ANF) concentration was determined in spontaneously hypertensive rats (SHR) and their control, Wistar-Kyoto (WKY) rats. CaCl2 10.5 mg (0.095 mmol) in 0.54 ml 5% glucose or an equal volume of vehicle alone was infused intravenously for 30 minutes into conscious precannulated SHR (vehicle, n = 16; CaCl2, n = 16) and WKY rats (vehicle, n = 25; CaCl2, n = 15). Direct systolic blood pressure was measured throughout the infusion period. Blood samples for serum total calcium and plasma ANF were obtained at the end of each experiment. The systolic blood pressure did not change significantly during infusion of the vehicle or CaCl2 in either strain. No significant difference was observed in serum total calcium concentration between SHR and WKY rats after vehicle (9.8 +/- 0.1 [mean +/- SEM] mg/dl vs. 10.0 +/- 0.1) or after CaCl2 infusion (12.2 +/- 0.3 vs. 12.2 +/- 0.2). Plasma ANF concentrations after both vehicle and CaCl2 infusion were significantly higher in SHR than in WKY rats (vehicle, 211 +/- 24 pg/ml vs. 129 +/- 11, p less than 0.05; CaCl2, 395 +/- 21 vs. 278 +/- 33, p less than 0.05). There were high degrees of correlation between serum total calcium and plasma ANF both in SHR (r = 0.77, p less than 0.001) and in WKY rats (r = 0.76, p less than 0.001). No significant difference was observed in the slopes of the regression lines of ANF as a function of the serum total calcium concentration between SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium binding capacity of erythrocyte membrane in human hypertension.
Authors: Cirillo M , Trevisan M , Laurenzi M
Published: June 2012

The cell membrane calcium binding capacity of genetically hypertensive rats is reduced when measured in the presence of the submicromolar calcium concentrations proper of intracellular environment. The present work, performed as an ancillary study to an epidemiological survey on an entire population, aimed to investigate the existence of a similar abnormality in human hypertension. Calcium binding to the erythrocyte membrane was measured in clinically healthy normotensive (n = 12) and hypertensive individuals (n = 24). For this purpose, a filtration technique was used, based on the determination of 45Ca bound to the erythrocyte membrane in the presence of free calcium concentrations (40 nmol/l and 1 mumol/l), which are similar to those of the intracellular environment. The intra-assay technical error was determined on 35 duplicate samples and, when expressed as percent of the mean, was 24.1 at the 40 nmol/l concentration and 16.8 at the 1 mumol/l concentration. Membranes of untreated hypertensive patients, at both calcium concentrations, bound significantly less calcium than the control group. Treated and untreated hypertensive individuals had comparable values of membrane calcium binding capacity. Membranes of the treated hypertensive group bound less calcium than those of the normotensive group at both calcium concentrations, but the difference was statistically significant only in the presence of 40 nmol/l free calcium. A significant positive correlation was observed between the calcium binding capacity at 40 nmol/l concentration and that at 1 mumol/l in the treated and untreated hypertensive groups (r = 0.73 and 0.75, respectively; 0.51 for the normotensive group). These findings support the hypothesis that a cell membrane abnormality is detectable in some hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of hypertension on aortic atherosclerosis in the Watanabe rabbit.
Authors: Chobanian A V , Lichtenstein A H , Nilakhe V , Haudenschild C C , Drago R , Nickerson C
Published: June 2012

The effects of one-kidney, one clip Goldblatt hypertension on aortic atherosclerosis have been studied in the Watanabe heritable hyperlipidemic (WHHL) rabbit. Renovascular surgery was performed on WHHL rabbits at 3 months of age, and the rabbits were followed for periods of 3-6 months. Aortic atherosclerosis was assessed by measurement of intimal surface involvement with atherosclerotic lesions, determination of aortic free and ester cholesterol content, and microscopic examination. Systolic blood pressure increased by approximately 40-60 mm Hg in the renovascular surgical group as compared with the sham-operated group, but body weight, heart rate, serum cholesterol, and serum triglyceride were unaffected. Aortic atherosclerosis was increased in the hypertensive rabbits, even after 2-3 months of hypertension. At 3 months after renovascular surgery, the aortic surface area covered by atherosclerotic disease averaged 77 +/- 4.4% in hypertensive as compared with 16 +/- 3.3 in control rabbits. At 6 months after surgery, the values were 62 +/- 8.2% and 30 +/- 5.3% in the hypertensive and control rabbits, respectively. The differences in surface involvement and cholesterol content as a result of hypertension were particularly prominent in the descending thoracic aorta. Atherosclerotic lesions in the descending thoracic and abdominal aortic regions of normotensive WHHL rabbits were localized primarily to the ostia of branch vessels, but in the hypertensive rabbits, the involvement was typically very diffuse. No major differences in the nature of atherosclerotic lesions of comparable size were apparent by light microscopy. The results indicate that hypertension accelerates atherogenesis in the WHHL rabbit and suggest that this model may be valuable for studying the mechanisms by which such acceleration is induced.
Blood pressure in four remote populations in the INTERSALT Study.
Authors: Carvalho J J , Baruzzi R G , Howard P F , Poulter N , Alpers M P , Franco L J , Marcopito L F , Spooner V J , Dyer A R , Elliott P
Published: June 2012

Four remote population samples (Yanomamo and Xingu Indians of Brazil and rural populations in Kenya and Papua New Guinea) had the lowest average blood pressures among all 52 populations studied in INTERSALT, an international cooperative investigation of electrolytes and blood pressure. Average systolic blood pressure was 103 versus 120 mm Hg in the remaining INTERSALT centers; diastolic blood pressure in these four population samples averaged 63 versus 74 mm Hg in the 48 other centers. There was little or no upward slope of blood pressure with age; hypertension was present in only 5% of the rural Kenyan sample and virtually absent in the other three centers. Also in marked contrast with the rest of the centers was level of daily salt intake, as estimated by 24-hour urinary sodium excretion. Median salt intake ranged from under 1 g to 3 g daily versus more than 9 g in the rest of INTERSALT populations. Average body weight was also low in these four centers, with no or low average alcohol intake, again unlike the other centers. The association within these four centers between the above variables and blood pressure was low, possibly reflecting their limited variability. While several other INTERSALT centers also had low average body weight or low prevalence of alcohol drinking, when this was accompanied by much higher salt intake (7-12 g salt or 120-210 mmol sodium daily), hypertension prevalence ranged from 8% to 19%. These findings confirm previous reports that in populations with a low salt intake, there is little or no hypertension or rise of blood pressure with age.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced responsiveness to angiotensin II in vascular smooth muscle cells from spontaneously hypertensive rats is not associated with alterations in protein kinase C.
Authors: Resink T J , Scott-Burden T , Baur U , Bürgin M , Bühler F R
Published: June 2012

This study compares vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats with respect to protein kinase C and intracellular responses to angiotensin II (Ang II). Ang II-induced degradation of polyphosphoinositides and accumulation of inositol di- and tris-phosphates was enhanced (approximately twofold) in hypertensive-derived cells, without a change (vs. normotensive-derived cells) in half-maximally effective concentrations of Ang II. Intracellular pH (approximately 6.6) was comparable between both cell isolates at quiescence, but alkalinization induced by Ang II, serum, or phorbol ester was greater (delta 0.1-0.2 pH units) for hypertensive-derived cells. For both cell types, the intracellular pH response to these agonists was prevented in the presence of Na+-H+ exchange inhibitors. S6 kinase activation induced by Ang II was enhanced (approximately twofold) in hypertensive-derived cells, whereas activation in response to serum or 12-O-tetradecanoylphorbol 13-acetate did not differ significantly between the two cell types. Quantitation of protein kinase C by immunoblotting and [3H]phorbol dibutyrate binding procedures revealed no differences between the two smooth muscle cell isolates (at quiescence or in the presence of serum) with respect to either total amounts or subcellular distribution. Sensitivity of protein kinase C to phorbol ester was apparently also not different between the two cell types, as assessed from dose-dependent (phorbol ester) S6 kinase activation profiles. Phorbol ester caused a similar subcellular redistribution of [3H]phorbol dibutyrate binding in the two cell isolates, but for both, minimal (10%) translocation occurred in response to Ang II. The data suggest that enhanced agonist responsiveness in vascular smooth muscle cells is unlikely to involve alterations in protein kinase C.
Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Miyauchi T , Ishikawa T , Tomobe Y , Yanagisawa M , Kimura S , Sugishita Y , Ito I , Goto K , Masaki T
Published: June 2012

Endothelin, an endothelium-derived vasoconstrictor peptide, and angiotensin II were intravenously injected into the femoral vein of normotensive Wistar-Kyoto (WKY) rats that had been anesthetized with urethane. Blood pressure and heart rate were recorded from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. Endothelin showed a potent, dose-dependent pressor action. The dose-response relations for the increase in blood pressure of rats receiving endothelin were comparable with those of rats receiving angiotensin II. However, endothelin showed far more long-lasting effects. Endothelin-induced responses consisted of three phases: a rapid and transient depressor phase and then two phases of pressor (transient and long-lasting) response. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+ channel blocker, markedly attenuated the slow phase of the pressor response but only slightly attenuated the rapid one. The pressor action of endothelin was not inhibited by continuous infusions of saralasin, which almost abolished the angiotensin II-induced pressor response. Endothelin-induced pressor response was also not attenuated by indomethacin, a prostaglandin synthesis inhibitor. These data provide evidence that endothelin produces a unique, potent, and long-lasting pressor response, which appears to be in part related to the activation of Ca2+ channels. In 12-week-old spontaneously hypertensive rats (SHR), the maximal pressor response to endothelin was slightly but significantly greater than that in age-matched WKY rats, but the dose dependency of the response was approximately consistent with that in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Age and hypertension promote endothelium-dependent contractions to acetylcholine in the aorta of the rat.
Authors: Koga T , Takata Y , Kobayashi K , Takishita S , Yamashita Y , Fujishima M
Published: June 2012

This study was undertaken to compare age-related changes in endothelium-dependent vascular responses in both hypertensive and normotensive rats. Aorta from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) aged 4-6 weeks (young), 3-6 months (adult), and 12-25 months (old) were examined for relaxation to acetylcholine, adenosine 5'-triphosphate (ATP), and sodium nitroprusside. Rubbed (endothelium denuded) aorta from all groups displayed neither relaxation nor contraction to acetylcholine. Maximal relaxation responses to acetylcholine were reduced progressively with increasing age in unrubbed aorta of both SHR and WKY rats. In addition, acetylcholine caused not only dose-dependent relaxations at lower concentrations but also increases in tension at higher concentrations in unrubbed aorta of old WKY rats as well as adult and old SHR. However, indomethacin completely inhibited the tension development. As a result, aorta treated with indomethacin demonstrated similar acetylcholine-induced, endothelium-dependent relaxations in all groups. The thromboxane A2 synthetase inhibitor (E)-7-phenyl-7-(3-pyridyl)-6-heptanoic acid (CV-4151) partially but significantly depressed the increases in tension in aorta of old WKY rats. The degrees of endothelium-dependent relaxations to ATP and endothelium-independent relaxations to sodium nitroprusside were almost similar in all groups. These findings suggest that the release of or vascular responsiveness to endothelium-derived relaxing factor in the aorta is well maintained through senescence in both strains and that, in the aorta of not only SHR but also old normotensive WKY rats, the endothelium releases contracting factors that may be thromboxane A2 and other vasoconstrictor prostanoids.
Altered pituitary hormone response to naloxone in hypertension development.
Authors: McCubbin J A , Surwit R S , Williams R B , Nemeroff C B , McNeilly M
Published: June 2012

Endogenous opioid regulation of blood pressure is altered during stress in young adults at risk for hypertension. We studied the effects of the opioid antagonist naloxone on the secretion of corticotropin and beta-endorphin during psychological stress in young adults with mildly elevated casual arterial pressures. Naloxone-induced secretion of both corticotropin and beta-endorphin was significantly diminished in persons at enhanced risk for hypertension compared with the low blood pressure control group. Results suggest that opioidergic inhibition of anterior pituitary function is altered in hypertension development.
Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.
Authors: Clozel J P , Kuhn H , Hefti F
Published: June 2012

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.
Ultrastructure of hypertensive rat aorta. Increased basement membrane-like material.
Authors: Guyton J R , Dao D T , Lindsay K L , Taylor A A
Published: June 2012

To determine the effect of elevated blood pressure on the ultrastructure of rat aorta, hypertension (average mean pressure 163 +/- 17 mm Hg) was produced by suprarenal aortic coarctation. After 3 weeks, the subendothelium of the hypertensive thoracic aorta showed significantly increased volume measurements for mononuclear leukocytes and basement membrane-like material compared with the sham-operated control group. Focal areas of rarefaction of the subendothelial extracellular material were associated with the nearby presence of mononuclear leukocytes. None of these alterations were found in the normotensive abdominal aorta. The tunica media of hypertensive thoracic aorta also contained significantly increased basement membrane-like material. This new finding in an animal hypertension model is the direct result of the quantitative morphological approach employed in this study. In some rats, the partially constricting aortic ligature compromised the right renal artery leading to ischemic atrophy of the right kidney and hyperreninemia in addition to hypertension. In this group, excluded from the previous analysis and evaluated separately, subendothelial thickening and accumulation of basement membrane-like material in the thoracic aorta were greatly increased compared with the control group and other hypertensive rats. This result could not be attributed to an effect of blood pressure alone and might have been caused in part by humoral factors. Basement membrane accumulation appears to be an important early response of the arterial wall to hypertension or other factors in this rat model.
Na(+)-H+ antiport activity in skin fibroblasts from blacks and whites.
Authors: Hatori N , Gardner J P , Tomonari H , Fine B P , Aviv A
Published: June 2012

The predisposition of black people to salt (NaCl)-sensitive essential hypertension may relate to racial differences in cellular Na+ metabolism. This tenet was investigated by examining the Na(+)-H+ antiport in serially passed skin fibroblasts from blacks and whites. Na(+)-dependent stimulation of the Na(+)-H+ antiport by cellular acidification resulted in a greater maximal velocity (Vmax) (mean +/- SEM) of this transport system in quiescent fibroblasts from blacks than fibroblasts from whites; the Vmax for recovery from cellular pH (pHi) of 6.6 was 5.84 +/- 0.50 versus 4.39 +/- 0.34 mmol H+/l X 20 seconds for blacks and whites, respectively (p less than 0.05). Although the Na+ concentration producing 50% stimulation of the Na(+)-H+ antiport for blacks (35.1 +/- 5.7 mM) was greater than for whites (24.1 +/- 3.5 mM), this difference was not statistically significant. No racial differences were observed in the Hill coefficient (n, 1.35 +/- 0.21 for blacks and 1.46 +/- 0.28 for whites). Compared with whites, cells from blacks exhibited a greater response to cytoplasmic acidification over the range of pHi values 6.20-6.60, as exhibited by an augmented rate of recovery in the pHi. These differences were not due to different basal pHi values or cellular buffering capacities, which were similar for blacks and whites. Na(+)-H+ antiport activity was not correlated with family history of hypertension. Increased activity of the Na(+)-H+ antiport in fibroblasts from blacks was confirmed without cellular acidification by stimulating quiescent cells with 10% human serum. This study demonstrates innate racial differences in cellular membrane Na(+)-H+ antiport activity.
Prostanoids and aldosterone-induced mild experimental hypertension in rats.
Authors: Hui R T , Grose J H , Lebel M , Falardeau P
Published: June 2012

The goal of this study was to determine the role of prostanoids in a new model of mineralocorticoid-dependent hypertension induced by the subcutaneous infusion of aldosterone (1 micrograms/hr) to normal male Sprague-Dawley rats. This regimen caused a mild and gradual increase in systolic pressure over a period of 4 weeks (113 +/- 1 vs. 137 +/- 3 mm Hg) and was associated with an increase in the in vivo formation of prostaglandins I2 and E2 and of thromboxane A2 in the kidney. High sodium intake induced a fall in the urinary levels of prostaglandin E2 and a rise in the arterial pressure of control rats (126 +/- 1 vs. 113 +/- 1 mm Hg) but did not influence aldosterone-induced hypertension. Indomethacin (3.0 mg/kg/day) caused a profound inhibition of the in vivo synthesis of prostaglandin I2 and thromboxane A2 without modifying the renal production of prostaglandin E2. Although indomethacin exerted no effect on aldosterone-induced hypertension in rats fed a normal diet, it caused a further rise in systolic pressure in aldosterone-treated rats fed a high sodium diet (157 +/- 6 vs. 140 +/- 4 mm Hg). The results of this study in a model of aldosterone-induced mild hypertension in the rat indicate that 1) aldosterone exerts a stimulatory effect on the renal synthesis of prostanoid, particularly prostaglandin E2; 2) thromboxane A2 and prostaglandin I2 do not seem to play a role in aldosterone-induced hypertension under conditions of normal dietary salt intake, whereas the role of prostaglandin E2 is unclear; 3) there is enough sodium in a normal diet to allow for the maximal expression of the hypertensive effect of aldosterone; 4) prostaglandin I2 seems to play a significant role in modulating the cardiovascular impact of a high sodium diet in aldosterone-treated rats; and 5) the renal biosynthesis of prostaglandin E2 is particularly resistant to the inhibitory effect of indomethacin in vivo.
Captopril improves hypertension and cardiomyopathy in rats with pheochromocytoma.
Authors: Hu Z W , Billingham M , Tuck M , Hoffman B B
Published: June 2012

Hypertension and cardiomyopathy are prominent findings in humans and rats harboring pheochromocytomas, tumors that can secrete enormous quantities of catecholamines. We have previously found that alpha- and beta-adrenergic receptor antagonists may ameliorate the hypertension and cardiomyopathy found in New England Deaconess Hospital rats implanted with pheochromocytoma. The present studies were designed to determine the possible action of the angiotensin converting enzyme inhibitor captopril on these changes in rats harboring pheochromocytomas. Rats were implanted with transplantable pheochromocytomas and treated with captopril dissolved in the drinking water (1 mg/ml) for 4-6 weeks. Systolic blood pressure was monitored by using the tail-cuff technique. In the rats with pheochromocytoma, blood pressure progressively increased to 184 +/- 3 mm Hg after the tumor was implanted. However, in rats with pheochromocytoma treated with captopril in the drinking water before the development of hypertension, blood pressure did not increase (137 +/- 3 mm Hg). In rats with pheochromocytoma with established hypertension, captopril normalized the systolic blood pressure. Plasma norepinephrine was markedly elevated to a similar extent in both groups compared with unimplanted control rats. Plasma renin activities were slightly lower in rats with pheochromocytoma compared with unimplanted control rats. Treatment with captopril of rats with pheochromocytoma did not modify contraction of isolated rings of thoracic aorta exposed in vitro to either phenylephrine or angiotensin II. Treatment with captopril markedly attenuated the cardiomyopathy induced by pheochromocytoma. These results demonstrate that captopril prevents the development of hypertension despite markedly elevated concentrations of catecholamines. In addition, captopril attenuates catecholamine-induced cardiomyopathy in pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit.
Authors: Chobanian A V , Haudenschild C C , Nickerson C , Drago R
Published: June 2012

The effects of 9 months of orally administered captopril (25-50 mg/kg body wt/day) on aortic atherosclerosis was examined in normotensive Watanabe heritable hyperlipidemic rabbits. Captopril caused a significant decrease in aortic atherosclerosis. Total aortic surface involvement by lesions was reduced from 48 +/- 3.6% in control Watanabe rabbits to 30 +/- 3.9% with captopril treatment (p less than 0.01). Most of the decrease could be accounted for by a marked reduction in atherosclerosis of descending thoracic aortas from 49 +/- 5.2% to 15 +/- 3.9% in control and captopril-related groups, respectively (p less than 0.001). Significant decrease in cholesterol content of descending thoracic aorta was also observed in captopril-treated rabbits. Microscopic examination of the arterial lesions in captopril-treated animals suggested a relative decrease in cellularity and increase in extracellular matrix as compared with untreated animals. These studies indicate that captopril has a potent antiatherosclerotic action in the Watanabe heritable hyperlipidemic rabbit.
Decreased cytosolic calcium and prostaglandin synthesis in prehypertensive rats.
Authors: Craven P A , Studer R K , DeRubertis F R
Published: June 2012

The capacity of cultured renal medullary interstitial cells derived from Dahl salt-sensitive and salt-resistant rats to synthesize prostaglandin E2 (PGE2) was compared. Basal and arginine vasopressin (AVP)-induced PGE2 production by interstitial cells from salt-resistant rats was fourfold to fivefold higher than corresponding values of those from the salt-sensitive rats. Similarly, basal and AVP-responsive release of [3H]arachidonate were twofold higher by interstitial cells from salt-resistant compared with salt-sensitive rats. Differences in PGE2 production were abolished by the calcium inophore A23187 or the addition of exogenous arachidonate. The latter findings suggested a role for altered availability of endogenous arachidonate, possibly mediated by reduced calcium-responsive lipase activity. Basal and AVP-induced increases in cytosolic free calcium concentration, assessed by the aequorin method, were significantly lower in interstitial cells from salt-sensitive versus salt-resistant rats, further supporting a possible role for altered cellular calcium homeostasis. Studies of the potential contribution of various phospholipases and of triglyceride lipase to the release of arachidonate for PGE2 synthesis in interstitial cells implicated phospholipase A2 activity as a major pathway. When assessed in vitro in cell cytosolic fractions at identical calcium concentration, phospholipase A2 activity was lower in interstitial cells from salt-sensitive versus salt-resistant rats. Thus, both reduced cytosolic free calcium and phospholipase A2 activity of interstitial cells from salt-sensitive rats may contribute to the diminished capacity of these cells to liberate endogenous arachidonate for PGE2 synthesis.
Effect of dietary salt on the skeletal muscle microvasculature in Dahl rats.
Authors: Boegehold M A , Kotchen T A
Published: June 2012

The purpose of this study was to identify microvascular alterations that could contribute to increased peripheral vascular resistance in the Dahl salt-sensitive rat with salt-induced hypertension. Intravital microscopy was used to study the spinotrapezius muscle arteriolar network in anesthetized salt-sensitive rats fed either a high salt (7% sodium chloride) or low-normal salt (0.45% sodium chloride) diet for 4 weeks. Age-matched Dahl salt-resistant rats on high and low-normal salt diets served as controls. The high salt diet had no effect on arterial pressure in salt-resistant rats but increased arterial pressure in salt-sensitive rats. Mean resting diameter of arcade arterioles in salt-sensitive rats on high salt diet was reduced by 25% compared with salt-sensitive rats on low salt or salt-resistant rats on either diet. After abolition of vascular tone with 10(-3) M adenosine, arcade diameters were comparable in all groups. No difference among groups was found in either resting or passive diameter of the more distal transverse arterioles. Measurement of vessel lengths and numbers in cleared muscle specimens revealed no differences among groups in the anatomic density of either arcade or transverse arterioles. These data suggest that a reduction in the resting diameter of arcade, but not transverse, arterioles may increase spinotrapezius muscle vascular resistance in hypertensive salt-sensitive rats. The similarity in vascular densities among groups indicates that structural rarefaction of arterioles does not contribute to any increase in spinotrapezius muscle resistance at this stage of salt-induced hypertension.
Body fat and its distribution in relation to casual and ambulatory blood pressure.
Authors: Gerber L M , Schnall P L , Pickering T G
Published: June 2012

This study was undertaken to evaluate the associations of body fat and its distribution with casual and ambulatory blood pressure in nonobese men. One hundred and thirty-five normotensive or mildly hypertensive (but untreated) men employed at three work sites were studied. Casual blood pressure was measured at the work site at initial screening and on a second occasion by a nurse. Ambulatory blood pressure was measured noninvasively for 24 hours on a workday and analyzed as work, home, and sleep blood pressure measurements. Anthropometric measurements included height, weight, and waist and hip circumferences. Blood pressure was highest while at work; home blood pressure was higher than screening blood pressure or nurse blood pressure, and sleep blood pressure was lowest. Weight and both waist and hip circumferences (but not their ratio) were all significantly correlated with screening, nurse, and sleep blood pressures but not with work or home blood pressures. Stepwise regression analysis showed that waist circumference was the best overall predictor of blood pressure. We suggest that in situations where blood pressure is the dependent variable, correlations with other variables may be closest for "basal" measures of blood pressure and may be obscured by the effects of daily activities on blood pressure.
Chronic hyperinsulinemia and blood pressure. Interaction with catecholamines?
Authors: Hall J E , Brands M W , Kivlighn S D , Mizelle H L , Hildebrandt D A , Gaillard C A
Published: June 2012

Although hyperinsulinemia and increased adrenergic activity have been postulated to be important factors in obesity-associated hypertension, a cause and effect relation between insulin, catecholamines, and hypertension has not been established. The aim of this study was to determine whether chronic hyperinsulinemia, comparable with that found in obese hypertensive patients, causes hypertension in normal dogs, increases plasma catecholamines, or potentiates the blood pressure effects of norepinephrine. In six normal dogs, insulin infusion (1.0 milliunits/kg/min) for 7 days, with euglycemia maintained, increased fasting insulin fourfold to sixfold. However, mean arterial pressure did not increase, averaging 99 +/- 2 mm Hg during the control period and 91 +/- 3 mm Hg during the 7 days of insulin infusion. Insulin did not alter plasma norepinephrine or epinephrine, which averaged 171 +/- 27 and 71 +/- 14 pg/ml, respectively, during the control period and 188 +/- 29 and 45 +/- 12 pg/ml during the 7 days of insulin infusion. In six dogs, norepinephrine was infused (0.2 microgram/kg/min) for 7 days to raise plasma norepinephrine to 2,940 +/- 103 pg/ml. Insulin infusion (1.0 milliunits/kg/min) for 7 days during simultaneous infusion of norepinephrine did not further increase mean arterial pressure, which averaged 101 +/- 3 during norepinephrine and 98 +/- 2 mm Hg during insulin plus norepinephrine infusion. Thus, chronic hyperinsulinemia did not increase mean arterial pressure or plasma catecholamines and did not potentiate the blood pressure actions of norepinephrine. These observations provide no evidence that chronic hyperinsulinemia or interactions between insulin and plasma catecholamines cause hypertension in normal dogs.
Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients.
Authors: Jones S L , Trevisan R , Tariq T , Semplicini A , Mattock M , Walker J D , Nosadini R , Viberti G
Published: June 2012

A familial predisposition to arterial hypertension has recently been suggested as one important component of the susceptibility to diabetic kidney disease. Sodium-lithium countertransport activity, a marker of risk for essential hypertension, has been found to be increased in diabetic patients with overt nephropathy. We have measured red blood cell sodium-lithium counter-transport activity in 36 microalbuminuric insulin-dependent diabetic patients, a group at high risk of progression to clinical nephropathy and cardiovascular disease, and compared it with that of a matched group of 36 normoalbuminuric diabetic patients. Sodium-lithium countertransport was higher in the microalbuminuric (0.43 [95% confidence interval (CI) 0.38-0.47] mmol/l red blood cells [RBC]/hr) than in the normoalbuminuric diabetic patients (0.29 [0.25-0.33] mmol/l RBC/hr, mean difference 0.14 [0.08-0.20]; p less than 0.0001). Microalbuminuric patients had a higher frequency of parental hypertension than normoalbuminuric diabetic patients (56% vs. 28%, p less than 0.05). Sodium-lithium countertransport was related to mean arterial pressure in the microalbuminuric patients (r = 0.54, p less than 0.001) and to daily insulin requirements in both groups (microalbuminuric patients r = 0.39, p less than 0.05; normoalbuminuric patients r = 0.42, p less than 0.01). In a subset of patients in whom lipoproteins were measured, sodium-lithium countertransport activity was related to total and very low density lipoprotein triglycerides (r = 0.41, p less than 0.05 and r = 0.48, p less than 0.05) and to apolipoprotein B (r = 0.56, p less than 0.05), independently of body mass index, albumin excretion rate, glycemic control, and insulin dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet activating factor and one-kidney, one clip hypertension.
Authors: Cotter J L , Vandongen R , Burton D L , Sturm M J
Published: June 2012

The reduction in blood pressure to normotensive levels within 3 hours of unclipping the one-kidney, one clip Goldblatt hypertensive rat has been attributed to the release of potent blood pressure-lowering lipids, one of which is thought to be identical to platelet activating factor. The specific platelet activating factor receptor antagonist WEB 2086 was infused intravenously into hypertensive one-kidney, one clip rats, and the mean arterial blood pressure changes after unclipping were examined. Before infusion, blocking doses of WEB 2086 were confirmed to effectively abolish the fall in blood pressure induced by exogenous platelet activating factor. Serotonin release in response to exogenous platelet activating factor was also inhibited in platelets preincubated with plasma from rats infused with the antagonist. Hypertensive rats were given a bolus blocking dose of WEB 2086 (5 mg/kg i.v.) and the same dose by infusion (5 mg/kg/hr i.v.) before they were unclipped. A control group was given a bolus volume of saline and infused with saline before unclipping. In WEB 2086-treated rats, blood pressure fell from a baseline mean of 181 +/- 13.0 to 125 +/- 23 mm Hg after 4 hours, a fall of 28%. Saline-treated rats fell from a mean of 194 +/- 23 to 127 +/- 25 mm Hg (33%). There was no significant difference in the blood pressure fall between the two groups. Therefore, platelet activating factor is unlikely to be responsible for the restoration of normal blood pressure after unclipping the Goldblatt hypertensive rat. We attribute the fall in blood pressure to other presently unidentified renomedullary lipids.
Ventricular relaxation of diabetic spontaneously hypertensive rat.
Authors: Davidoff A J , Pinault F M , Rodgers R L
Published: June 2012

Diabetes, and possibly the hypothyroidism that attends diabetes, impairs mechanical relaxation of ventricular muscle, in part by depressing the rate of Ca2+ uptake by sarcoplasmic reticulum. Left ventricular hypertrophy exacerbates the adverse effects of diabetes on cardiac performance, but its effects on relaxation variables have not been well characterized. We examined the impact of streptozotocin-induced diabetes (8 weeks) on ventricular pressure load-dependent relaxation and sarcoplasmic reticular calcium uptake of hearts from spontaneously hypertensive rats and Wistar-Kyoto rats. Subsets of diabetic hypertensive rats were treated with either insulin (10 units/kg/day) or triiodothyronine (8-10 micrograms/kg/day). Diabetes impaired load-dependent relaxation and depressed sarcoplasmic reticular calcium uptake only in spontaneously hypertensive rat hearts. Either insulin or triiodothyronine treatment prevented the diabetes-induced depressions of both mechanical and biochemical indexes of relaxation. The results suggest that 1) hypertrophic ventricles of spontaneously hypertensive rats are more susceptible to the detrimental effects of diabetes on relaxation indexes than are the nonhypertrophic Wistar-Kyoto rat ventricles, and 2) the hypothyroidism that attends diabetes may contribute to the impaired relaxation of diabetic spontaneously hypertensive rat left ventricle.
Potassium channels and vascular reactivity in genetically hypertensive rats.
Authors: Furspan P B , Webb R C
Published: June 2012

In hypertension, membrane potassium permeability and vascular reactivity are increased. This study characterizes a potassium-selective channel and contractions to barium, a potassium channel inhibitor, in vascular smooth muscle (tail artery) from spontaneously hypertensive stroke-prone rats (SHRSP) and normotensive Wistar-Kyoto (WKY) rats. Smooth muscle cells were isolated by enzymatic digestion, and potassium channel activity was characterized by using patch-clamp technique (inside-out configuration). Isometric contractile activity was evaluated in helically cut arterial strips by using standard muscle bath methodology. In membrane patches, a voltage-gated, calcium-insensitive, potassium-selective channel of large conductance (200 picosiemens) was observed. The channel did not conduct sodium or rubidium. Barium (10(-6) to 10(-4) M) produced a dose-dependent blockade of channel activity. These channel characteristics did not differ in SHRSP and WKY rat cells. After treatment with 35 mM KCl, barium (10(-5) to 10(-3) M) caused greater contractions in SHRSP arteries compared with arteries in WKY rats. The contractions to barium were markedly attenuated in calcium-free solution, and nifedipine and verapamil abolished contractions induced by barium in depolarizing solution. We conclude that increased vascular reactivity to barium in SHRSP arteries is not due to an alteration in the biophysical properties of the potassium channel studied.