bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal abnormalities in normotensive insulin-dependent diabetic offspring of hypertensive parents.
Authors: Hannedouche T P , Marques L P , Natov S , Delgado A G , Boitard C , Lacour B , Grünfeld J P
Published: June 2012

To assess the effects of genetic predisposition of essential hypertension on early renal function in recent insulin-dependent diabetics, we studied inulin, para-aminohippuric, sodium, and lithium clearances in 69 unselected diabetics with (n = 20) and without (n = 49) a family history of essential hypertension. Despite similar metabolic control, glomerular filtration rate and mean arterial pressure were significantly higher in diabetics with than in those without a family history of hypertension. However, no difference was found between the two groups regarding renal vascular resistance, sodium excretion, or fractional proximal and distal sodium reabsorption. Renal responses to acute captopril (75 mg) administration were evaluated in 27 patients (six with family history of hypertension). Captopril decreased filtration fraction and mean arterial pressure similarly in both groups, whereas glomerular filtration rate and renal vascular resistance decreased more dramatically in diabetics with family history of hypertension. These findings indirectly suggest an abnormal response to angiotensin of vascular tone in recent diabetics with familial predisposition to hypertension. Renal response to acute nicardipine (2.5 mg i.v.) administration was analyzed in 24 patients (five with family history of hypertension). In both groups, nicardipine similarly decreased mean arterial pressure and renal vascular resistance and induced a marked natriuretic effect due to a predominant reduction in proximal reabsorption of sodium. However, the increase in sodium excretion was twofold to threefold more pronounced in diabetics with a family history of hypertension. Whether these early renal abnormalities may contribute to the risk of diabetic nephropathy, as suggested by retrospective studies, remains to be determined.
Phospholipase C responses in cells from spontaneously hypertensive rats.
Authors: Osanai T , Dunn M J
Published: June 2012

We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.
Pressure independence of renin release by isolated kidneys of Lyon hypertensive rats.
Authors: Medeiros I A , Vincent M , Benzoni D , Sassard J
Published: June 2012

In the present work the influence of perfusion pressure on renal functions and renin release was studied before and after the blockade of thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors using isolated kidneys from 7-week-old genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strain. Kidneys were single pass perfused with Krebs-Henseleit solution with a gelatine derivative (Polygeline) added as an oncotic agent. A servocontrolled system stabilized the renal perfusion pressure (RPP) at any chosen (+/- 1 mm Hg) level. In baseline conditions (RPP, 90 mm Hg), LH (n = 7) kidneys differed from LN (n = 6) and LL (n = 8) controls by increased vascular resistance, decreased glomerular filtration rate, and natriuresis. The LH kidney responses to stepwise changes in RPP (between 60 and 170 mm Hg) differed from those of LN and LL rats by a significantly lower perfusion flow, glomerular filtration rate, and natriuresis. Above all, the reduction in RPP, which induced a marked and highly reproducible renin release in LN and LL kidneys, was devoid of effects in LH kidneys. The blockade of TXA2/PGH2 receptors by AH23848 (4 x 10(-6) M) did not change the baseline (RPP, 90 mm Hg) functions of kidneys of the three strains. During changes in RPP, the responses of LN and LL kidneys were not modified, whereas LH kidneys exhibited significant increases in both glomerular filtration rate and natriuresis. Finally, AH23848 significantly decreased the renin release by kidneys of the three strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Sympathetic modulation of endothelium-derived relaxing factor.
Authors: Pegoraro A A , Carretero O A , Sigmon D H , Beierwaltes W H
Published: June 2012

To determine whether the release of endothelium-derived relaxing factor (EDRF) is sympathetically mediated, we studied the effects of beta-blockade by propranolol, ganglionic blockade with hexamethonium, or mechanical pithing on the blood pressure response to EDRF inhibition in anesthetized rats. We inhibited EDRF with 10 mg/kg of either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine-methyl ester (L-NAME). In controls, L-NMMA and L-NAME increased blood pressure by 14 +/- 1 (p less than 0.01) and 22 +/- 2 mm Hg (p less than 0.01), respectively. Propranolol lowered blood pressure from 98 +/- 3 to 72 +/- 4 mm Hg without altering the response to L-NAME (delta 26 +/- 3). This response correlated with the resting blood pressure (r = 0.87; p less than 0.001). Hexamethonium (25 mg/kg) lowered blood pressure from 118 +/- 6 to 85 +/- 4 mm Hg but did not change the response to L-NMMA (delta 15 +/- 1). In pithed rats, blood pressure was lowered, but the pressor response to L-NAME was unchanged. When blood pressure was returned to normotensive levels by angiotensin II, norepinephrine, or phenylephrine, L-NAME increased blood pressure by 50 +/- 2, 68 +/- 8, and 109 +/- 7 mm Hg, respectively (p less than 0.001). We conclude that an intact autonomic nervous system is not needed for the pressor response to EDRF inhibition. The enhanced response in pithed rats treated with vasoconstrictors may be due to removal of the buffering effect of the baroreceptors and the absence of EDRF, which would oppose vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Salt-dependent hypertension in the sinoaortic-denervated rat.
Authors: Osborn J W , Provo B J
Published: June 2012

To determine the extent to which baroreceptor function is a determinant of salt-dependent hypertension, we studied the cardiovascular and renal responses to increasing dietary sodium chloride in sinoaortic-denervated (n = 9) and sham-denervated (n = 9) Sprague-Dawley rats. Rats were instrumented with an arterial catheter for measurement of arterial pressure and were individually housed for daily measurements of water intake, sodium intake, urinary output, and urinary sodium excretion. Arterial pressure was monitored daily over a 30-minute period by computer. After 3 days of control measurements (0.4% sodium chloride diet), dietary sodium chloride was increased to 8.0% for 21 days, followed by a 3-day recovery period (0.4% sodium chloride). Ingestion of an 8.0% sodium chloride diet resulted in a 20- to 25-fold increase in sodium intake and a fivefold increase in water intake in both groups. In sinoaortic-denervated rats, arterial pressure increased approximately 10 mm Hg on days 5-10, 20 mm Hg on days 11-18, and 30 mm Hg on days 19-21 of 8.0% sodium chloride. Arterial pressure returned to control levels within the first 24 hours of the recovery period. Elevated sodium intake had no significant effect on arterial pressure in the sham-denervated group. Finally, there were no significant differences between groups in urine output or urinary sodium excretion at any time during the study. We conclude that a primary impairment in the afferent limb of the arterial baroreceptor reflex results in salt-dependent hypertension in the Sprague-Dawley rat.
Pressure-induced activation of membrane K+ current in rat saphenous artery.
Authors: Berczi V , Stekiel W J , Contney S J , Rusch N J
Published: June 2012

Pressurization of isolated arteries may result in Ca(2+)-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K+ channels is augmented by rises in cytosolic Ca2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K+ channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca(2+)-free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K+ channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16 +/- 1 mV) than at 25 mm Hg (10 +/- 1 mV). The sensitivity of K+ current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K+ current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6-fold by the Ca2+ ionophore A23187 (10 microM), suggesting a Ca2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K+ channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction.
Effects of a nonpeptide vasopressin antagonist (OPC-21268) on cytosolic Ca2+ concentration in vascular and cardiac myocytes.
Authors: Matsui H , Kohmoto O , Hirata Y , Serizawa T
Published: June 2012

A selective V1 antagonist, 1-(1-[4(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2(1 H)- quinolinone (OPC-21268), which is nonpeptide and orally effective, has been recently synthesized. We studied the effects of vasopressin and OPC-21268 on cell contraction with a video motion detector and cytosolic Ca2+ concentration ([Ca2+]i) by using indo-1 in cultured rat vascular smooth muscle cells and cultured chick embryo ventricular myocytes. Exposure of cultured vascular smooth muscle cells to vasopressin (1-100 nM) dose-dependently produced an initial transient increase (from control level [Ca2+]i of 133.6 +/- 10.9 nM to peak [Ca2+]i of 842.7 +/- 172.8 nM at 100 nM vasopressin, p less than 0.01) and then a small sustained increase in [Ca2+]i. After pretreatment of vascular smooth muscle cells with 1 microM OPC-21268, the effects of 100 nM vasopressin on [Ca2+]i were abolished. Exposure of ventricular myocytes to 100 nM vasopressin slightly but significantly decreased peak systolic cell position (-8.7 +/- 3.7%, p less than 0.05) and also produced reductions in peak systolic [Ca2+]i (from 962.2 +/- 76.4 to 751.2 +/- 70.5 nM, p less than 0.01) within 30 seconds. Pretreatment of ventricular myocytes with OPC-21268 (1 microM) completely suppressed vasopressin-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that vasopressin may increase vascular tone and may also cause a direct negative inotropic effect via V1 receptors and that this orally active V1 antagonist (OPC-21268) may have potential clinical usefulness.
Role of nitric oxide in renal papillary blood flow and sodium excretion.
Authors: Mattson D L , Roman R J , Cowley A W
Published: June 2012

Renal medullary interstitial infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) decreased papillary blood flow to 71 +/- 5% of control without altering outer cortical flow. Before NG-nitro-L-arginine infusion, interstitial acetylcholine administration (200 micrograms/hr) increased cortical and papillary blood flow to 134 +/- 6% and 113 +/- 2% of control, respectively. After NG-nitro-L-arginine administration, the vasodilator response to acetylcholine was abolished. In clearance experiments, renal medullary infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) significantly decreased total renal blood flow by 10%, renal interstitial fluid pressure by 23%, sodium excretion by 34%, and urine flow by 39% without altering glomerular filtration rate, fractional sodium and water excretion, blood pressure, or urine osmolality. These data indicate that selective inhibition of nitric oxide in the renal medullary vasculature reduces papillary blood flow, which is associated with decreased sodium and water excretion. We conclude that nitric oxide exerts a tonic influence on the renal medullary circulation.
Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats.
Authors: Dai F X , Skopec J , Diederich A , Diederich D
Published: June 2012

Vascular resistance is increased in the kidneys of spontaneously hypertensive rats (SHR). Previous studies have demonstrated impaired vascular relaxations of mesenteric resistance arteries of SHR because of increased production of a cyclooxygenase-dependent endothelium-derived contracting factor. To test the hypothesis that altered endothelial function contributes to the enhanced constriction in kidneys of SHR, endothelium-mediated relaxations of renal resistance arteries from 5-6-week-old prehypertensive SHR and Wistar-Kyoto rats were compared in arteriographs. Acetylcholine induced endothelium-dependent contractions in SHR arteries, while potent endothelium-dependent relaxations were noted in renal arteries from Wistar-Kyoto rats. Inhibition of cyclooxygenase (indomethacin) or blockade of prostaglandin H2-thromboxane A2 receptors (SQ 29,548) blocked acetylcholine-induced contractions in SHR renal arteries; relaxations in SHR renal arteries after either treatment were similar to those observed in renal arteries from Wistar-Kyoto rats. NG-Nitro-L-arginine inhibited acetylcholine-mediated relaxations in both SHR and Wistar-Kyoto arteries. Endothelium-independent relaxations induced by verapamil were comparable in SHR and Wistar-Kyoto arteries. Thus, the impaired response to acetylcholine in SHR renal resistance arteries may result from the release of endothelium-derived cyclooxygenase products (prostaglandin H2 or thromboxane A2), which oppose endothelium-derived nitric oxide-mediated relaxation.
Sequential hemodynamic changes in end-stage renal disease and the anephric state during volume expansion.
Authors: Kim K E , Onesti G , DelGuercio E T , Greco J , Fernandes M , Eidelson B , Swartz C
Published: June 2012

The sequence of hemodynamic events during periods of salt- and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase in BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in five patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt- and water-loading increased the BP. It is concluded that during salt- and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt- and water-loading in patients deprived of renal excretory function.
Mechanism of enhanced blood pressure rise after reclipping following removal of a renal artery clip in rats.
Authors: ten Berg R , de Jong W
Published: June 2012

The effect of removing a renal artery clip 14 to 18 days after its application was studied in two-kidney, one clip hypertensive rats. Blood pressure decreased to a normotensive level within 24 hours after the removal of the clip. The cardiovascular effects of reapplication of the clip and infusion of renin, angiotensin II, and norepinephrine were assessed at that time. Reapplication of the clip to the unclipped renal artery was followed in 1 hour by an increase in blood pressure to the level of sham-operated renal hypertensive rats. After reapplication of the clip, plasma renin activity increased to the same level as after the initial application. Application of the clip to the contralateral renal artery did not affect blood pressure and failed to increase plasma renin activity. It appears that renin release is a prerequisite for the rapid rise of blood pressure after reapplication of the clip. The infusion of renin, angiotensin II, and norepinephrine for 90 minutes caused an enhanced blood pressure response similar to that observed following reapplication of the clip. The increase in blood pressure in control rats was associated with bradycardia, which was absent in unclipped rats. The enhanced response of unclipped rats to an infusion of renin was abolished by pithing. It is concluded that removal of a renal artery clip unmasks a hyperreactivity of the cardiovascular system to reapplication of the clip.
Inhibition of angiotensin II potentiation of sympathetic nerve activity by beta-adrenergic antagonists.
Authors: Jackson E K , Campbell W B
Published: June 2012

Since beta-adrenergic blockers are effective in the therapy of hypertension by a mechanism related to the degree of activation of the renin-angiotensin system, the effect of eight beta blockers was examined on angiotensin II potentiation of nerve stimulation (NS) in isolated perfused rat mesenteric vessels. The vasoconstrictor response to periarterial NS was obtained by monitoring changes in perfusion pressure while a beta blocker or a beta blocker and angiotensin II (3 ng/ml) were added to the perfusate. Although each beta blocker tended to decrease responses to NS, in the concentrations used, only metoprolol significantly inhibited responses to NS. Angiotensin II, when infused alone, potentiated the responses to NS by 63% (p less than 0.01). These enhanced responses following angiotensin II were inhibited in a dose-related manner (10--300 ng/ml) by beta 1, beta 2, and mixed beta blockers. At the 100 ng/ml concentration, DL-propranolol, timolol, metoprolol, practolol, butoxamine, and H35/25 inhibited the angiotensin II potentiation of NS by 83%, 76%, 77%, 59%, 72%, and 41% respectively. The order of potency for this action was as follows: timolol = metoprolol = butoxamine greater than propranolol greater than practolol greater than H35/25. Administration of D- and L-propranolol also reduced the responses by 75%. The vasoconstrictor responses to injected norepinephrine (NE), in the presence and absence of angiotensin II, were not altered by DL-propranolol or timolol. In conclusion, beta-adrenergic blockers were found to interfere with the effect of angiotensin II on the sympathetic neuron, a property that could contribute to the antihypertensive action of these drugs.
Characterization of postsynaptic alpha-adrenergic receptors by [3H]-dihydroergocryptine binding in muscular arteries from the rat mesentery.
Authors: Colucci W S , Gimbrone M A , Alexander R W
Published: June 2012

Alpha-adrenergic receptors are likely to be important determinants of the effects of catecholamines on vascular resistance. To study the alpha-adrenergic receptor in muscular arteries of the type that determine vascular resistance, we characterized and quantitated alpha-adrenergic receptors in a particulate fraction of the highly reactive, richly innervated arteries of the rat mesentery. With the ligand [3H]-dihydroergocryptine ([3H]-DHEC), specific binding (displaceable by 5 microM phentolamine) is saturable. There is a single class of binding sites with a dissociation constant (Kd) of 2.9 nM and a maximal binding capacity of 68 fmoles of [3H]-DHEC per mg of particulate fraction protein. Catecholamines compete for [3H]-DHEC binding stereospecifically and with the alpha-adrenergic potency series of (-)epinephrine greater than (-)norepinephrine greater than (-)isoproterenol. Binding is rapid (t 1/2 less than or equal to 2 mins) and rapidly reversible (t 1/2 less than or equal to 2 mins). Inhibition of [3H]-DHEC binding by the alpha-adrenergic antagonist phentolamine (Kd = 3.0 nM) is much greater than by the beta-adrenergic antagonist propranolol (Kd = 8200 nM). The alpha 1-selective antagonist prazosin (Kd = 63 nM) is 20 times more potent in competing for [3H]-DHEC binding than is the alpha 2-selective antagonist yohimbine (Kd = 1250 nM), thus suggesting that the alpha-adrenergic receptor identified is predominantly of the alpha 1 subtype that is responsible for vascular smooth muscle contraction. This extension of radioligand binding techniques to highly innervated muscular arteries of the type contributing to vascular resistance will allow the study of the role of the vascular alpha-adrenergic receptor in various physiologic states and models of hypertension.
Possible role of phosphorylation-dephosphorylation in the regulation of calcium metabolism in cardiovascular tissues of SHR.
Authors: Bhalla R C , Sharma R V , Ramanathan S
Published: June 2012

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were compared for phosphorylation-dephosphorylation mechanism(s) in aorta, caudal artery, inferior vena cava, and right and left ventricles. Reduction of cAMP-induced phosphorylation of microsomes and cAMP-dependent protein kinase activity was significant in the aorta and caudal artery of SHR compared with WKY. These changes were not observed in the vena cava of SHR. Phosphoprotein phosphatase activity was significantly increased (p less than 0.05) in the soluble fraction of arterial smooth muscle. No changes were observed, however, in the myocardium or vein. Furthermore, the extent of phosphorylation, and Ca2+ uptake ability and the protein kinase activity in the soluble and the microsomal fractions were not reduced in the myocardium of SHR compared with WKY. These data suggest that phosphorylation-dephosphorylation mechanisms are altered in the microsomal fraction of the aorta and caudal artery of SHR, which may result in reduced Ca2+ uptake by the intracellular organelle. The changes observed could have a significant effect on vasodilatation of arteries in the hypertensive state. The lesion appears specific to the arterial smooth muscle in the cardiovascular tissues.
A survey of patterns of nonpharmacologic care for hypertensive patients, including recommendations for their children.
Authors: Soltero I , Tsong Y , Cooper R , Stamler J , Stamler R , Garside D
Published: June 2012

To ascertain current approaches of physicians to nutritional-hygienic management of hypertensive patients and their children, a survey was done among a random sample of Chicago-area generalists, internists, and cardiologists. Thirteen items related to advice for patients; two for their children. Of 713 physicians holding M.D. degrees in the sample, 573 (80%) responded. For hypertensive patients, the great majority of physicians indicated that they advise weight loss, avoidance of salt use at table, no smoking, regular exercise, limitation of alcohol intake, and avoidance of stressful situations. Although 98% advised weight loss, a minority responded positively to reduction of carbohydrate and/or fat intake. Only 25% recommended limiting the salt use of children, and only 19% recommended taking the blood pressure of children of hypertensive patients. These data indicate that the majority of Chicago-area practitioners advocate nutritional-hygienic measures for their hypertensive patients. Only a minority, however, apparently advocate primary preventive approaches for the children of hypertensive patients.
Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat.
Authors: Katholi R E , Naftilan A J , Oparil S
Published: June 2012

In many experimental models, acute increases in sympathetic nervous system activity produce disproportionately greater vasoconstriction in the renal vascular bed than occurs in most other vascular beds. Since increased sympathetic nervous system activity has been implicated in the pathogenesis of DOCA-salt hypertension in the rat, we hypothesized that an attenuation of renal sympathetic tone would delay the development of this form of hypertension. Renal denervation was carried out in 5-week-old uninephrectomized male Sprague-Dawley rats 1 week before beginning DOCA-salt treatment. Systolic blood pressures using the tailcuff method in 32 sham-operated rats were significantly (p less than 0.05) elevated above control by Day five (115 +/- 3 vs 128 +/- 3 mm Hg) of DOCA-salt administration and continued to rise, reaching a plateau by Day 21 (192 +/- 5 mm Hg). In contrast, DOCA-salt administration in 32 renal denervated rats did not result in a significant elevation of blood pressure above control until Day 17 (121 +/- 3 vs 135 +/- 3 mm Hg, p less than 0.05). During the first 2 weeks of DOCA-salt treatment, fractional urinary sodium excretion was significantly greater (p less than 0.05) in renal denervated rats than in sham animals. During the third week of DOCA-salt administration, renal denervated rats had a rapid rise in blood pressure and a fall in fractional urinary sodium excretion to the level of the sham-operated animals. Coincident with the development of hypertension was a threefold increase in renal norepinephrine content (5.3 +/- 0.4 ng/g on Day 14 vs 17.7 +/- 3.0 ng/g on Day 24, p less than 0.01), suggesting reinnervation. These data suggest that increased renal sympathetic tone in the DOCA-salt rat facilitates sodium retention and is necessary for the development of the hypertension.
Pressor responsiveness to vasopressin in the rat with DOC-salt hypertension.
Authors: Crofton J T , Share L , Wang B C , Shade R E
Published: June 2012

To further characterize the role of vasopressin in DOC-salt hypertension, four groups of unilaterally nephrectomized rats were studied: control rats given no further treatment, rats treated with DOC and given 1% saline to drink, or rats treated with only DIC or 1% saline had similar pressor responses to exogenous vasopressin and angiotensin II. Within the DOC-salt group, two populations of rats were identified: one with normal pressor responsiveness to vasopressin, and one with markedly enhanced pressor responsiveness to vasopressin. Incidence of enhanced responsiveness increased with duration of treatment. Urinary excretion of vasopressin was elevated in the 1% saline and DOC-salt groups after 1 week of treatment, and in the DOC group after 4 weeks. However, the plasma vasopressin concentration was elevated only in the rats treated with both DOC and saline. It is suggested that vasopressin is essential for the expansion of blood volume in the early stages of DOC-salt hypertension, and functions as a direct pressor agent only in the later stages.
Direct radioimmunoassay of human renin: comparison with renin activity in plasma and amniotic fluid.
Authors: Guyene T T , Galen F X , Devaux C , Corvol P , Menard J
Published: June 2012

Human plasma and amniotic liquid were activated by dialysis at pH 3.3. Then, renin before and after acidification was determined by two methods: enzymatic activity measurement, and direct radioimmunoassay. The identity between nonactivated and activated renin in plasma and amniotic fluid on the one hand, and pure renin on the other, was demonstrated by the dilution curves in radioimmunoassay. After acidification, mean plasma renin activity in 17 patients with high renin activity rose from 26.8 +/- 11.7 pmoles A I ml-1 h-1 to 67.9 +/- 29.3 pmoles A I ml-1 h-1, whereas the mean renin concentration tested by direct radioimmunoassay remained constant at 13.8 +/- 10.5 and 14.8 +/- 11.2 fmol/ml before and after acidification respectively. In amniotic fluid, renin activity increased from 9.7 to 227 pmoles angiotensin I/ml/h, but the renin concentration did not change. Direct radioimmunoassay of renin may therefore be considered as measuring total renin, regardless of its enzymatic activity. In 12 hypertensive patients undergoing bilateral renal-vein catheterization, the direct measurement of renin was very significantly correlated to the non-activated (r = 0.883) and activated renin values (r = 0.963).
Subcellular distribution and storage form of rat renal renin.
Authors: Sagnella G , Price R , Peart W
Published: June 2012

The subcellular distribution and nature of rat renal renin has been investigated by means of analytical subcellular fractionation and gel filtration on Sephadex G-100. During differential centrifugation, renin activity was recovered mainly in soluble and heavy mitochondrial fractions. On sucrose gradient centrifugation in either a conventional or in a B XIV zonal rotor, renin activity equilibrated at 1.54 M sucrose and was partially resolved from marker enzymes for mitochondria (succinate dehydrogenase), lysosomes (acid phosphatase), plasma membranes (alkaline phosphatase), and peroxisomes (catalase). On gel filtration of the soluble or extracts of the renin-granular fractions on Sephadex G-100, renin activity eluted as a single peak with an apparent molecular weight (MW) of 42,000; no change in activity was found when these fractions were acidified to pH 3.0. When kidney homogenates were prepared in the presence of the proteolytic inhibitor N-ethylmaleimide (NEM, 10 mM), whereas the renin from the granular fractions displayed a MW of 44,000, that from the soluble fraction was apparently higher (69,000). Addition of NEM (10 mM) to the soluble fraction previously shown to contain only the low MW form of renin also resulted in an apparently high MW form of renin. These results indicate that rat renal renin is associated with a mechanically fragile, distinct type of subcellular organelle. Renin within this structure is of the low MW form and is not acid activatable. The soluble fraction, however, contains a factor(s) that, in the presence of NEM, combines with the low MW renin to form a complex of apparently high MW.
Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension.
Authors: Crantz F R , Swartz S L , Hollenberg N K , Moore T J , Dluhy R G , Williams G H
Published: June 2012

We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in diastolic blood pressure (DBP, -13 +/- 2.5 mm Hg), angiotensin II (-7.1 +/- 2.1 pg/ml), and plasma renin activity (PRA, +6.6 +/- 1.9 ng/ml/hr) (p < 0.01 in all cases). Twenty-one patients receiving SQ 14,225 had significant changes in mean DBP (-18 +/- 1.5 mm Hg), angiotensin II (-6.6 +/- 1.5 pg/ml), and PRA (+7.8 +/- 2.4 ng/ml/hr) (all p values < 0.01). In spite of a significantly greater hypotensive response (p < 0.02), patients receiving SQ 14,225 showed increments in PRA and decrements in angiotensin II that did not differ significantly from those seen after SQ 20,881. Moreover, there was a significant change in plasma kinins in patients receiving SQ 20,881 (+2.0 +/- 0.9 ng/ml, p < 0.01) but no change in kinins in patients receiving SQ 14,225 (0.0 +/- 0.1, ns). We conclude that there are important differences in the mechanism mediating the hypotensive response to SQ 20,881 and SQ 14,225 in normal renin essential hypertension.
Effects of short-term norepinephrine infusion on plasma catecholamines, renin, and aldosterone in normal and hypertensive man.
Authors: Beretta-Piccoli C , Weidmann P , Meier A , Grimm M , Keusch G , Glück Z
Published: June 2012

The acute responsiveness of plasma catecholamine, renin (PRA), and aldosterone levels to exogenous norepinephrine was studied under placebo conditions and following renin (PRA), and aldosterone levels to exogenous norepinephrine was studied under placebo conditions and following renin-angiotensin activation by diuretic pretreatment in 25 normal subjects and 34 patients with borderline-to-moderate essential hypertension. Norepinephrine infusion caused increases in plasma norepinephrine (PNE) that correlated with the infused norepinephrine dose (p < 0.001); this relationship was similar in normal and hypertensive subjects and unaltered by diuretic therapy. Plasma epinephrine and dopamine levels were unchanged during norepinephrine infusion. Norepinephrine infusion at pressor doses stimulated PRA (p < 0.01). The PRA responses correlated with the dose of infused norepinephrine (p < 0.0025), and norepinephrine-stimulated PRA correlated with basal PRA (p < 0.001). These norepinephrine-PRA relationships were unaltered by diuretic treatment and similar in normal and hypertensive subjects. In both groups, norepinephrine also caused a similar increase in plasma aldosterone (p < 0.05) under placebo conditions, but not following diuretic therapy. These findings demonstrate that an acute increase in the blood levels of the adrenergic neurotransmittor, norepinephrine, causes mild but distinct stimulation of plasma renin and aldosterone levels. Renin release in response to exogenous norepinephrine is not enhanced following renin-angiotensin activation by diuretic pretreatment. The responsiveness of the renin-angiotensin-aldosterone system to an acute norepinephrine input seems to be intact in essential hypertension.
Proline and thymidine uptake in rabbit ear artery segments in vitro increased by chronic tangential load.
Authors: Hume W R
Published: June 2012

Indices of structural change were examined in blood vessel walls subjected to increased tangential load in a new, in vitro model system. Ring segments of rabbit ear artery were maintained in organ culture medium for times up to 9 days. Tangential load was chronically applied with small, intraluminal springs made of 0.010 in. diameter stainless steel wire. the applied load was considered to produce levels of circumferential wall tension corresponding to those induced by a range of levels of blood pressure. The indices of structural change examined were the uptake of radioactively-labelled proline and thymidine, which indicate protein synthesis and cell division respectively. Increased uptake of both proline and thymidine was noted in artery segments under elevated mechanical tension after a latency of 3 to 4 days. The degree of uptake was related to the degree of calculated wall tension elevation. The work indicated that cell division and protein synthesis can be induced in the blood vessel wall by increased wall tension alone, in vitro.
Effect of dietary salt on hemodynamics of established renal hypertension in the rabbit. Implications for the autoregulation theory of hypertension.
Authors: Korner P I , Oliver J R , Casley D J
Published: June 2012

Two groups of 10 rabbits were subjected to renal cellophane wrapping and sham operation. Their initial mean arterial pressures (MAP) were similar, 92 +/- 1.5 and 90 +/- 2.9 mm Hg. Six weeks later three experimental periods began, each of 2 weeks' duration, on low, normal, and high salt (1, 9, and 50 mmole Na/100 g food) diets. Each group had two subgroups: rabbits with both kidneys, and rabbits with only one kidney and previous nephrectomy. The hemodynamic findings were similar in each group. After sham operation, the range of dietary salt produced no significant circulatory changes. After wrapping, MAP was reduced on low compared with normal and high salt diets (122 vs 132 and 136 mm Hg; p = 0.01). This was entirely due to lowering of cardiac output (CO) on low salt; on normal and high salt CO was higher than in sham-operated rabbits. Total peripheral resistance (TPR) in the wrapped animals was unaffected by diet, i.e., 21.4, 20.5, and 21.2 units on low, normal, and high salt--about 35% above values of sham-operated rabbits. Volume-related CO changes therefore produce long-term changes in MAP without alteration in TPR, which is not in conformity with the autoregulation theory of hypertension. Evidence of impaired capacity of wrapped compared with sham-operated rabbits to handle salt included diet-related hematocrit changes, lower creatinine clearance, and some differences in renin responses to salt. Giving saralasin reduced TPR while the rabbits were on low salt; the fall was twice as great in wrapped compared with sham-operated rabbits.
Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril.
Authors: Bao G , Gohlke P , Qadri F , Unger T
Published: June 2012

The contribution of endogenous kinins to the chronic antihypertensive effect of angiotensin converting enzyme inhibitors was investigated in two-kidney, one clip hypertensive Wistar rats, using the new bradykinin B2-receptor antagonist HOE 140 (D-Arg, [Hyp3, Thi5, D-Tic7, Oic8]-bradykinin). In a first protocol, rats were pretreated orally with the angiotensin converting enzyme inhibitor ramipril (1 mg/kg per day), for 4 weeks. Acute blockade of bradykinin receptors by intravenous injections of HOE 140 at doses of 8.4 and 100 micrograms/kg, which inhibited the depressor responses to exogenous bradykinin, did not affect the antihypertensive effect of ramipril in these animals. Bradykinin receptors were then blocked chronically by subcutaneous infusion of HOE 140 (500 micrograms/kg per day) via osmotic minipumps for 6 weeks, while ramipril treatment was continued. HOE 140 partially reversed the antihypertensive effect of ramipril from 115.3 +/- 4.6 to 123.8 +/- 3.3 mm Hg (mean arterial blood pressure) after 3 weeks and to 121.3 +/- 2.9 mm Hg after 6 weeks. In contrast, in controls (ramipril plus subcutaneous vehicle infusion) mean arterial blood pressure decreased further from 112.0 +/- 6.0 to 110.3 +/- 4.9 mm Hg after 3 weeks and to 103.7 +/- 5.0 mm Hg after 6 weeks (p less than 0.05 and p less than 0.01, HOE 140 versus controls). Plasma catecholamines were not significantly different between the two groups at the end of the experiment, indicating that the partial reversal of the antihypertensive effect was not due to a bradykinin-like agonistic effect on catecholamine release.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute hyperinsulinemia induces sodium retention and a blood pressure decline in diabetes mellitus.
Authors: Gans R O , Bilo H J , Nauta J J , Heine R J , Donker A J
Published: June 2012

Hyperinsulinemia supposedly contributes to hypertension in diabetes mellitus. We sought to determine if the renal and cardiovascular effects of insulin are preserved in diabetes despite resistance to its glucose-lowering effect. We studied the effects of two doses of insulin (50 and 500 milliunits/kg.hr-1), using the euglycemic clamp technique, on fractional sodium excretion, blood pressure, and heart rate in two groups of non-insulin-dependent diabetics: eight patients with and eight patients without hypertension. Hypertensive diabetics had higher basal insulin levels than normotensive diabetics (21.8 +/- 2.9 and 14.4 +/- 1.6 milliunits/l, respectively [mean +/- SEM]; p = 0.03). The degree of insulin resistance, but not plasma insulin levels, correlated with the height of mean arterial blood pressure (r = 0.60 and 0.73 at the low and high insulin dose, respectively; p less than 0.05). In contrast, the change in mean arterial blood pressure correlated negatively with the change in endogenous insulin levels during the control experiment (r = -0.41, p less than 0.02). Exogenous insulin induced a similar reduction in fractional sodium excretion in normotensive and hypertensive diabetics (43 +/- 5.9% and 48 +/- 16.4% during the low insulin dose and 57 +/- 9.1% and 62 +/- 12.5% during the high insulin dose, respectively). A decline in blood pressure was noted that correlated with the whole body glucose uptake during the high insulin dose (r = 0.52, p less than 0.05). Since heart rate response and plasma norepinephrine level during the insulin clamp were comparable in both groups, an abnormality of the baroreceptor reflex is suggested. It appears that insulin resistance, but not insulin, is primarily related to hypertension. At the same time, insulin may still exert some effect on blood pressure by way of its renal or vasodilatory, or both, action.
Enhanced release of endothelium-derived relaxing factor in mineralocorticoid hypertension.
Authors: Bockman C S , Jeffries W B , Pettinger W A , Abel P W
Published: June 2012

Ring segments of superior mesenteric arteries studied in vitro were used to determine the role of the vascular endothelium in regulating vascular contractile and relaxant sensitivity in deoxycorticosterone acetate (DOCA)-salt hypertension. Wistar rats were given DOCA (20 mg/kg s.c. twice per week) and 1% NaCl drinking water for 5 weeks. In ring segments containing endothelium, there was a decrease in contractile sensitivity to arginine vasopressin, no change in contractile sensitivity to norepinephrine and KCl, and no change in relaxant sensitivity to acetylcholine or isoproterenol in arteries from hypertensive rats compared with normotensive controls. Removal of the vascular endothelium by rubbing had no effect on the contractile response to arginine vasopressin and KCl or the relaxant response to isoproterenol in control arteries. In arteries without endothelium, DOCA-salt hypertension caused a threefold increase in contractile sensitivity for arginine vasopressin, norepinephrine, and KCl; a 50% reduction in maximal relaxation to isoproterenol; and a threefold decrease in relaxant sensitivity to sodium nitroprusside. Indomethacin (10 microM) had no effect on contraction or relaxation. However, N-monomethyl L-arginine unmasked altered contractile sensitivity to norepinephrine in arteries from DOCA-salt hypertensive rats. These data show that the endothelium compensates for increased contractile and reduced relaxant responses of vascular muscle in DOCA-salt hypertension by increasing the release of endothelium-derived relaxing factor. These data suggest that altered vascular responsiveness is masked by the endothelium, thus preventing these alterations from contributing to increased peripheral resistance during the development of DOCA-salt hypertension.
Calcium channel activation in arterioles from genetically hypertensive rats.
Authors: Storm D S , Stuenkel E L , Webb R C
Published: June 2012

Enhanced contractile responsiveness to the calcium channel agonist Bay K 8644 has been documented in large conduit arteries and small muscular arteries from hypertensive rats. The present study examined the effects of Bay K 8644 on the intracellular calcium concentration ([Ca2+]i) in microvessels from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Using microspectrofluorometry of fura-2, [Ca2+]i was measured in smooth muscle cells localized on arteriolar fragments (15-35 microns external diameter) isolated after collagenase digestion of the pancreas. Resting [Ca2+]i in hypertensive arterioles (94 +/- 6 nM, n = 29) did not differ from that in normotensive vessels (81 +/- 4 nM, n = 40). KCl (50 mM), applied alone and in the presence of Bay K 8644 (30 nM), stimulated increases in [Ca2+]i that were reversed in calcium-free solution and with nifedipine (10 microM), consistent with activation of potential-operated calcium channels. Potassium-induced calcium transients were consistently potentiated by Bay K 8644. The change in [Ca2+]i evoked by KCl alone or in combination with Bay K 8644 did not differ between arterioles from hypertensive and normotensive rats. In 24% of the vessels from hypertensive rats and in 29% of those from normotensive rats, Bay K 8644 evoked an increase in [Ca2+]i that did not differ significantly between the two strains. The findings indicate that, in contrast to observations made in larger arteries, there is no evidence of a functional abnormality in potential-operated calcium channels in very small arterioles from genetically hypertensive rats.
Increased waist/hip ratio, metabolic disturbances, and family history of hypertension.
Authors: Widgren B R , Herlitz H , Wikstrand J , Sjöström L , Berglund G , Andersson O K
Published: June 2012

To test whether nonhypertensive subjects with a two-generation positive family history of hypertension (PFH) are characterized by disturbed glucose metabolism, 16 men (38 +/- 6 years old) with PFH and 25 subjects matched for age and with negative family histories of hypertension (NFH) were recruited. Blood pressure; serum lipids; erythrocyte transmembrane sodium transport; and the glucose, plasma insulin, and C-peptide responses to an oral glucose tolerance test were investigated. Subjects with PFH had higher blood pressure, body weight, body mass index (BMI), waist/hip ratio (WHR), and abdominal sagittal diameter than subjects with NFH. Baseline blood glucose, plasma insulin, serum lipids, and transmembrane sodium transport did not differ between the two groups. Blood glucose levels at 90 and 120 minutes after oral glucose were significantly higher in subjects with PFH than in controls. Blood glucose adjusted for BMI and WHR at 90 minutes was significantly related to a PFH. Plasma insulin level at 90 minutes during the glucose load was significantly higher in subjects with PFH. In multivariate analysis, WHR was significantly related to baseline blood pressure, insulin, and cholesterol, whereas BMI was significantly associated with the insulin response to the oral glucose tolerance test. Transmembrane sodium transport was significantly related to blood pressure only. In conclusion, subjects with PFH are characterized by increased body weight and BMI, increased visceral fat accumulation, and an altered blood glucose response to an oral glucose load. It was also shown that WHR was related to blood pressure and that BMI was more related to cholesterol and response to glucose loading than a PFH was.