口服L-精氨酸对腹主动脉缩窄后大鼠血压、心肌肥厚和血管舒张功能的影响

本文利用缩窄大鼠腹主动脉的方法制备高血压模型，观察了正常大鼠、未服和口服Ｌ－精氨酸两周的腹主动脉狭窄的大鼠的血压、心肌肥厚及血管舒张功能的改变，旨在了解Ｌ－精氨酸对腹主动脉缩窄性高血压大鼠的作用。研究发现腹主动脉狭窄后大鼠发生了严重的高血压及心肌肥厚。未服Ｌ－精氨酸的大鼠心肌肥厚，且血管环对１０－８～１０－５ｍｏｌ／Ｌ乙酰胆碱诱导的舒张反应明显减低；而Ｌ－精氨酸口服治疗两周能减轻其心肌肥厚，并部分改善乙酰胆碱诱导的血管舒张功能，但两组大鼠腹主动脉缩窄后的血压均升高，两者相比较差别无统计学意义（Ｐ＞０．０５）。结果提示：Ｌ－精氨酸（１０－５～１０－３ｍｏｌ／Ｌ）有直接舒张该大鼠血管环的作用，且呈剂量依赖关系，长期口服Ｌ－精氨酸可减轻腹主动脉缩窄性大鼠的心肌肥厚，改善其血管的舒张功能，而其血压的变化与上述作用无关。     

口服L-精氨酸对腹主动脉缩窄后大鼠血压、心肌肥厚和血管舒张功能的影响

本文利用缩窄大鼠腹主动脉的方法制备高血压模型，观察了正常大鼠，未服和口服Ｌ－精氨酸两周的腹主动脉狭窄的大鼠的血压，心肌肥厚及血管舒张功能的改变，旨在了解Ｌ－精氨酸对腹计劝缩窄性高血压大鼠的作用，研究发现腹主动脉狭窄后大鼠发生了肥厚，且血管环对１０＾－８￣１０＾－５ｍｏｌ／Ｌ乙酰胆碱诱导的舒张反应明显减低，而Ｌ－精氨到口服治疗两周舒张功能，但两组大鼠腹主动脉缩窄后的血压均升高，两者相比较差别无统计学     

Abnormal ion and water composition of veins and normotensive arteries in coarctation hypertension in rats.

We examined the water, sodium, and potassium composition of the thoracic aorta, abdominal aorta (plus iliac arteries), and veins (vena cava and portal vein) from rats with aortic coarctation. The aortas of 10 rats (group A) were coarcted above the renal arteries to produce hypertension. Control groups consisted of 10 rats sham-coarcted above and 10 rats coarcted below the renal arteries. In group A rats heart weights and carotid artery pressures were elevated over controls (P less than 0.01), whereas there were no significant differences in femoral arterial pressures. In group A rats both the hypertensive thoracic aorta and the normotensive abdominal aorta contained about 20% more water per unit of wet weight, and about 35% and 60% more sodium and potassium, respectively, per unit of dry weight than did the corresponding portions of aorta from control rats (P less than 0.01). In group A rats water (P less than 0.01), sodium (P less than 0.02), and potassium (P less than 0.05) contents of veins also were increased. There were no significant correlations between level of carotid arterial pressure and magnitude of changes in arterial and venous composition, nor were there significant differences between the magnitude of changes in the normotensive and hypertensive portions of the aorta. These results indicate that in rats abnormalities in vascular wall salt and water content are not necessarily a direct effect of the elevated pressure in hypertension.     

Hemodynamic consequences of left ventricular hypertrophy in spontaneously hypertensive rats.

Compared with hearts from normotensive rats isolated, perfused hearts from spontaneously hypertensive rats exhibit a rightward shift of the Frank-Starling curve in the lower range of filling pressures, that is, up to 10 mm Hg. The extent of this shift is proportional to the degree of left ventricular hypertrophy. This is suggested to be a consequence of an altered relation between end-diastolic pressure and end-diastolic tension of the progressively more thick-walled left ventricle. Furthermore, the cardiac function curves revealed that maximal cardiac performance is apparently better in spontaneously hypertensive rats than in normotensive rats at increased levels of afterload. Therefore, left ventricular hypertrophy in established hypertension seems to contribute to adjustment of cardiac performance to the enhanced pressure work in hypertension; however, this occurs at the expense of a rightward shift of the Frank-Starling curve. In spontaneously hypertensive rats studied in vitro, coronary vascular resistance per unit weight of tissue was increased at maximal dilation, as was maximal pressor response. This may reflect the same type of structural vascular adaptation that occurs in most systemic vascular beds in hypertension and that contributes to maintenance of increased vascular reactivity and flow resistance in both hypertensive patients and spontaneously hypertensive rats. Apparently as a consequence of this adaptation, splanchnic nerve stimulation at an increasing rate caused exaggerated increases in resistance in anesthetized hypertensive rats by comparison with findings in normotensive rats. However, the effect of capacitance vessel constriction on stroke volume caused by splanchnic nerve stimulation was less pronounced in hypertensive rats. This relative “hyporeactivity” of the capacitance vessels also suggests an altered relation between cardiac filling pressure and stroke volume of the hypertrophied left ventricle in the spontaneously hypertensive rat.     

Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction

To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.     

Renal function in rats with angiotensin II-salt-induced hypertension: effect of thromboxane synthesis inhibition and receptor blockade

This study was designed to assess the contribution of thromboxane (Tx) A2 to the pathogenesis of renal dysfunction in rats with angiotensin II (Ang II)-salt hypertension. Hypertension was induced in rats drinking 0.15 mol/l NaCl by infusion of Ang II (125 ng/min, intraperitoneally) for 12 days. Relative to values in water- and saline-drinking rats without Ang II infusion, rats with Ang II-salt hypertension exhibited increased renal vascular resistance, decreased renal blood flow, and increased renal excretion and glomerular synthesis of TxB2. Treatment with an inhibitor of TxA2 synthesis, UK 38,485, had no effect on renal function in normotensive and hypertensive rats. Similarly, the TxA2 and prostaglandin endoperoxide antagonist SQ 29,548 did not affect renal function in normotensive rats. In contrast, in rats with Ang II-salt hypertension of 12 days' duration, SQ 29,548 caused a reduction in renal vascular resistance, allowing for maintenance of renal blood flow in the face of an accompanying reduction in blood pressure. A comparable reduction in renal perfusion pressure, produced by constriction of the abdominal aorta above the renal arteries, was not accompanied by a reduction in renal vascular resistance in Ang II-salt hypertensive rats. Therefore, the SQ 29,548-induced lowering of renal vascular resistance is attributable not to renal blood flow autoregulation, but to blockade of the renal vasoconstrictor actions of TxA2 and/or prostaglandin endoperoxides. This interpretation implies that pressor eicosanoids contribute to increase renal vascular resistance in rats with severe Ang II-salt hypertension.     

Morphometric evidence for non-pressure-related arterial wall thickening in hypertension

To investigate the relation of pressure and vascular wall thickening in hypertension, we coarcted the abdominal aorta upstream to the renal arteries in 14 rats. Sham-coarcted (n = 16) and two-kidney, one-clip (Goldblatt) hypertensive rats (n = 13) served as controls. Tail, femoral, and carotid arterial pressures rose (p less than 0.01) in the two-kidney, one-clip hypertensives; only carotid pressure rose (p less than 0.01) in the coarcted rats, tail and femoral pressures remaining normal (p greater than 0.25). Thus, the hindquarters of the coarcted rats remained normotensive. Four to six weeks after surgery we perfusion-fixed vascular tissues of the hindquarters, including kidneys, with formalin at in vivo levels of pressure. Glycol methacrylate-embedded tissues were sectioned at 1 micron thickness and vessels quantitatively evaluated. The outer medial and lumen perimeters of abdominal aorta, femoral artery, and renal arterioles were measured; from these measurements, vessel outer and lumen diameters, medial thickness, medial area, and medial thickness-to-lumen radius ratios were calculated. Compared with sham-coarcted rats, abdominal aorta, femoral arteries, and renal arterioles less than 61 microns outer diameter in rats with coarctation and Goldblatt hypertension had significantly increased (up to +100%) medial area, medial thickness, and medial thickness-to-lumen radius ratios. In general, magnitudes of abnormalities were similar in Goldblatt and coarcted rats. Renal arterioles greater than 60 microns outside diameter in Goldblatt hypertensive, but not coarcted, rats also were thickened. These results indicate that vascular wall thickening occurs in conduit arteries and smaller renal arterioles in the normotensive hindquarters of coarcted rats, providing morphometric evidence for non-pressure-related mechanisms involved in vascular growth in this form of hypertension.     

Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells

In order to obtain information about the changes in lysosomal enzyme activities in arterial endothelial cells under hypertensive conditions, a biochemical study was performed on 5 lysosomal enzymes, acid phosphatase, N-acetyl-beta-glucosaminidase (NAGase), cathepsin B, cathepsin D and beta-glucuronidase, in endothelial cells isolated by an enzymatic technique from the aorta of spontaneously and renal hypertensive rats, and normotensive control rats. The aortic endothelial cells in the old spontaneously and the renal hypertensive rats showed increased activities of enzymes examined in comparison with those in the age-matched control rats. Endothelial cells in young spontaneously hypertensive rats did not show any elevated enzyme activities compared with those in the controls, and the enzyme activities tended to increase with aging. From this, it is deduced that hypertension activates lysosomal enzyme activities in aortic endothelial cells. The differences in the activities of NAGase, cathepsin B and cathepsin D between hypertensive and control animals increased markedly with advancing age. These activated lysosomal enzymes seem to be involved in the developmental mechanism of arterial endothelial cell injury in hypertension and in further development of hypertensive vascular changes.     

Dysfunction of the cholinergic anti-inflammatory pathway mediates organ damage in hypertension

Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the α7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. We tested the hypothesis that α7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation-induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the α7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and α7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the α7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor κB. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in α7nAChR(-/-) mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension.     

Angiotensin-converting enzyme activity of the aorta in experimental hypertensive rats

Angiotensin-converting enzyme activity of the aortic subcellular fractions (homogenate, mitochondria, microsomes and supernatant) was determined in normotensive and experimental hypertensive rats (1-clip, 1-kidney Goldblatt hypertensive; 1-clip, 2-kidney Goldblatt hypertensive and 2-clip, 2-kidney hypertensive rats). The systolic blood pressure markedly elevated in each group of experimental hypertensive rats, while it did not in normotensive rats. Angiotensin-converting enzyme activity was consistently high in the microsomal and supernatant fractions of the aorta in experimental hypertensive rats as well as in normotensive rats. However, the enzyme activity from each fraction of the aorta in 1-clip, 2-kidney Goldblatt hypertensive rats was significantly higher than that in normotensive and other experimental hypertensive rats. There was no significant difference in the enzyme activity among normotensive, 1-clip, 1-kidney Goldblatt hypertensive and 2-clip, 2-kidney hypertensive rats. The angiotensin-converting enzyme, widely distributed in subcellular fractions of the aorta, may play a possible role in the local control of vascular tone. It seems likely that increased angiotensin-converting enzyme activity in arterial tissue contributes to the initiation or development of hypertension in 1-clip, 2-kidney Goldblatt hypertension in rats.     

Eflornithine Alters Changes in Vascular Responsiveness Associated with Coarctation Hypertension

This study examined the temporal effects of the polyamine synthesis inhibitor eflornithine (alpha-difluoromethylornithine) on vascular responses to KCI, norepinephrine, sodium nitroprusside and acetylcholine in aortic rings from coarctation hypertensive rats. Coarctation hypertension reduced the contractile response of aortic rings to KCI and norepinephrine, increased sensitivity (reduced the EC₅₀ value) to norepinephrine and attenuated relaxation to acetylcholine by 14 days of hypertension. Treatment of coarctation hypertensive rats with eflornithine resulted in a normalization of the contractile intensity to KCI and norepinephrine and relaxations to acetylcholine by 14 days of hypertension. Responses to sodium nitroprusside were similar in all groups at all time points. Hyperresponsiveness to norepinephrine produced by coarctation of the aorta was not affected by eflornithine. These studies indicate that normalization of vascular function can occur in the presence of significantly elevated blood pressure upon chronic administration of eflornithine. This functional normalization correlates with eflornithine-mediated regression of structural abnormalities normally associated with pressure overload hypertension.     

Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension

Rabbits were rendered hypertensive by suprarenal coarctation of the abdominal aorta. Seven days later, endothelium-dependent and endothelium-independent vascular relaxations were examined in vascular rings taken from hypertensive (thoracic aorta, carotid artery) and normotensive (abdominal aorta) regions. Relaxation of phenylephrine-contracted rings in response to endothelium-dependent agonists (acetylcholine, A23187) was impaired, compared with that in sham-operated and intact controls, in regions exposed to the elevated blood pressure (i.e., above the coarctation). Responses to acetylcholine and A23187 in the abdominal aorta, below the coarctation, were not altered. The diminished endothelium-dependent responses in the thoracic aorta were not affected by pretreatment with the cyclooxygenase inhibitor indomethacin. In contrast to acetylcholine and A23187, responses to the endothelium-independent agonist nitroprusside were not attenuated in vessels from hypertensive regions, indicating that the defect occurred in the endothelium. The EC50 for acetylcholine-induced relaxations of thoracic aorta correlated significantly with mean arterial pressure above the coarctation, indicating that the extent to which endothelium-dependent relaxation is impaired is in proportion to the degree of blood pressure elevation. This study suggests that the diminished relaxations by endothelium-dependent agonists is a local response to the elevation of blood pressure and is not due to a circulating factor.     

Attenuated arteriolar dilator responses to calcium in genetically hypertensive rats

Vascular responses to calcium were studied in 14 genetically hypertensive (GH) rats of the New Zealand strain and 16 weight- and age-matched normotensive parent strain control rats under chloralose-pentobarbital anesthesia. Calcium (chloride or gluconate) in an isosmolar solution was infused intraarterially into the hindlimb vascular bed which was vascularly isolated, innervated, and pump-perfused (blood, 1 ml/min). Increases in limb plasma calcium concentrations up to 30 mEq/liter decreased limb vascular resistance, with no evidence for vasoconstriction. In GH rats decreases in limb vascular resistance in response to increments in limb plasma calcium concentrations of 3.6 to 10.8 mEq/liter were significantly (p less than 0.02) attenuated compared to age-matched controls. When responses in GH were compared to weight-matched controls, similar trends toward attenuation reached significance (p less than 0.02) at Ca2+ increments of 10.8 mEq/liter. In eight other GH rats, we measured total serum calcium concentrations and found them reduced (4.94 +/- 0.08 mEq/liter), especially as compared to values in eight rats of an unrelated Wistar strain (5.42 +/- 0.04 mEq/liter; p less than 0.05). These experiments provide evidence that, over physiological ranges, calcium relaxes arteriolar smooth muscle in rats and that this vasodilation is attenuated in genetically hypertensive rats. Thus, both the lower serum levels of calcium and the attenuated responses to calcium may contribute to the elevated peripheral vascular resistance and hypertension in these rats.     

Increased forearm vascular reactivity in patients with hypertension after repair of coarctation

To determine whether altered vascular reactivity could contribute to hypertension after repair of coarctation, the change in forearm and calf vascular resistances to small intra-arterial infusions of norepinephrine were measured in six patients who had undergone surgical correction of coarctation of the aorta but still had upper extremity hypertension and compared with similar measurements made in five normotensive patients with mild heart disease. Only the mean upper extremity pressure was significantly greater in the group that underwent repair of coarctation (102 +/- 11 vs 83 +/- 5 mm Hg, p less than .05, for mean arm pressures and 96 +/- 13 vs 83 +/- 7 mm Hg for mean leg pressures in patients who had coarctation vs normotensive patients, respectively). Forearm and calf blood flows were measured in the right arm and leg with a mercury-in-plastic strain-gauge plethysmograph. Forearm and calf vascular resistances were calculated by dividing mean arterial pressure of the appropriate extremity by the blood flow of that extremity. Norepinephrine was infused into the right brachial and femoral arteries of the patients at doses of 0.02, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7 microgram/min. Resting forearm and calf vascular resistances were similar in both groups of patients. The norepinephrine dose-response curves showed that control patients required more than three times the norepinephrine to produce the same percent increase in forearm vascular resistance (after 0.2 microgram/min forearm vascular resistance increased by 55% in the coarctation group, while the resistance in the control group increased by only 3%, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Overall hemodynamic pattern in coarctation of the abdominal aorta in conscious rats

This study was designed to examine the total body hemodynamics of abdominal aortic coarctation hypertension. The study quantitates both regional and organ blood flow and resistance in conscious rats both above and below an experimentally produced coarctation. The experimental group consisted of 10 male Sprague-Dawley rats with a mean pressure gradient of 68 mm Hg across the coarctation. This experimental group was compared with a group of eight control rats with no pressure gradient. Flow measurements were made with radioactively labeled microspheres 4 weeks after aortic constriction. This aortic coarctation produced an increase in cardiac index (22%) and total peripheral resistance (19%). Blood flow through tissues proximal to the coarctation was not different from control; vascular resistance was increased (31%). Flow through the tissues distal to the coarctation was increased (16%); vascular resistance was decreased (-22%). The upper carcass, diaphragm, and brain were the tissues most representative of flow above the coarctation, and the lower carcass and large intestine were the tissues most representative of flow below the coarctation. Coarctation of the aorta produced cardiac hypertrophy and increased microsphere shunting to the lungs.     

Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats

BACKGROUND AND OBJECTIVES: Epidemiologic studies indicate that ingestion of vegetables and fruit inhibits the development of cardiovascular disease. Chlorogenic acids are abundant phenolic compounds contained in vegetables and fruits, but the impact of dietary chlorogenic acids on vascular function in hypertension is not known. We therefore examined the effects of 5-caffeoylquinic acid (CQA), a representative chlorogenic acid, on blood pressure and vascular function in age-matched normotensive Wistar-Kyoto rats and spontaneously hypertensive rats. METHODS AND RESULTS: A single ingestion of CQA (30-600 mg/kg) reduced blood pressure in spontaneously hypertensive rats, an effect that was blocked by administration of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. When spontaneously hypertensive rats were fed diets containing 0.5% CQA for 8 weeks (approximately 300 mg/kg per day), the development of hypertension was inhibited compared with the control diet group. CQA ingestion increased urinary excretion of nitric oxide metabolites and decreased urinary excretion of hydrogen peroxide; decreased NADPH-dependent superoxide anion production in the aorta, suggesting that dietary CQA inhibited vascular NADPH oxidase activity; significantly improved acetylcholine-induced endothelium-dependent vasodilation in the aorta; and markedly reduced the degree of immunohistochemical staining for nitrotyrosine and media hypertrophy in aorta sections. In contrast, CQA had no effects in Wistar-Kyoto rats. CONCLUSIONS: Dietary CQA reduces oxidative stress and improves nitric oxide bioavailability by inhibiting excessive production of reactive oxygen species in the vasculature, and leads to the attenuation of endothelial dysfunction, vascular hypertrophy, and hypertension in spontaneously hypertensive rats.     

Coronary microvascular resistance in hypertensive cats.

Chronic systemic hypertension has been shown to alter the distribution of vascular resistance in many microvascular beds. The purposes of this study were to assess the effects of chronic systemic hypertension on the pressure distribution in the coronary microcirculation and to determine the microvascular site where coronary vascular resistance is increased. Cats were made hypertensive using a one-kidney, one-wrap model (Page model). A servonulling system was used to directly measure pressures in the epimyocardial microvessels of the beating left ventricle in normotensive and hypertensive cats. In chronically hypertensive cats, mean arterial pressure was 153 +/- 5 mm Hg compared with 98 +/- 3 mm Hg in normotensive cats (p less than 0.05). Left ventricular mass was increased approximately 34% in hypertensive cats (9.4 +/- 0.3 versus 7.0 +/- 0.3 g, p less than 0.05). Myocardial perfusion measured using radiolabeled microspheres was not different between hypertensive and normal cats. Coronary vascular resistance of the left ventricle was increased in hypertensive cats (0.90 +/- 0.08 versus 0.66 +/- 0.05 mm Hg x min x 100 g/ml, p less than 0.05). Microvascular pressures were measured in three groups of microvessels: small, less than 200 microns; medium, 200-300 microns; and large, greater than or equal to 300 microns. Mean microvascular pressures of large, medium, and small arterial microvessels in hypertensive cats were 144 +/- 8, 127 +/- 6, and 115 +/- 7 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension

Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.     

Effects of deuterium oxide (D2O) on the development of hypertension and Ca2+ homeostasis in spontaneously hypertensive rats

Increased calcium uptake in vascular tissues, leading to elevated cytosolic free calcium, has been implicated in the pathophysiology of hypertension. In this study we investigated the in vitro effect of deuterium oxide (D2O) on calcium uptake in Sprague-Dawley (SD) rat aortae as well as the effects of 25% D2O, orally administered to spontaneously hypertensive and Wistar-Kyoto (WKY) rats, on systolic blood pressure and aortic calcium uptake. The high calcium uptake induced by phenylephrine (50 mumols/l) via receptor-operated channels and by KCl (80 mmol/l) via voltage-operated channels in SD rat aortae was effectively reduced by D2O in a concentration-dependent manner. These results suggest that D2O, acting like a calcium channel blocker, effectively normalized vascular calcium uptake mechanisms. When, at 7 weeks of age, spontaneously hypertensive rats were given 25% D2O in their drinking water for a period of 6 weeks, the development of high systolic blood pressures and the associated increases in aortic calcium uptake were effectively prevented. D2O treatment did not affect blood pressures in normotensive WKY rats. The parallel increases in systolic blood pressure and in vascular calcium uptake suggest that increased calcium uptake mechanisms are associated with hypertension. Furthermore, D2O appears to prevent hypertension by normalizing calcium uptake in vascular smooth muscle.     

Failure of atriopeptin II to cause arterial vasodilation in the conscious rat

The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)