Influence of gender on control of arterial tone in experimental hypertension

1998 ◽  
Vol 275 (1) ◽  
pp. H15-H22 ◽  
Author(s):  
Mika Kähönen ◽  
Jari-Petteri Tolvanen ◽  
Kirsimarja Sallinen ◽  
Xiumin Wu ◽  
Ilkka Pörsti
Keyword(s):  
Study Groups ◽  
Experimental Hypertension ◽  
Relative Role ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
Adrenoceptor Agonist ◽  
Relaxation Responses ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

Endothelial dysfunction has been found to be less severe in female than in male spontaneously hypertensive rats (SHR), which could contribute to the gender differences observed in the extent and rate of progression of hypertension in SHR. However, the influence of gender on the roles of different endothelium-derived mediators in the arterial responses in hypertension have not been evaluated in detail. Therefore, contractile and relaxation responses of mesenteric arterial rings in vitro were studied in female and male SHR, with normotensive female and male Wistar-Kyoto rats (WKY) serving as controls. In norepinephrine (NE)-precontracted arterial rings, endothelium-dependent relaxations to ACh as well as endothelium-independent dilations to sodium nitroprusside were more pronounced in female than in male SHR, whereas relaxations to the β-adrenoceptor agonist isoproterenol remained equally impaired in female and male SHR. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, markedly enhanced the relaxations to ACh in male SHR but not in the other groups. The nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester attenuated the relaxations to ACh more effectively in female SHR and WKY than in the male groups. However, when endothelium-dependent hyperpolarization was prevented by precontracting the preparations with KCl, no significant differences were found in relaxations to ACh among the study groups. In conclusion, release of cyclooxygenase-derived constricting factors appeared to be more pronounced in male than in female SHR. In addition, the relative role of NO in endothelium-dependent arterial relaxation seemed to be higher in female than in male SHR, and relaxation induced by an NO donor also was more pronounced in female than in male SHR.

scholarly journals Nitroxyl donors retain their depressor effects in hypertension

2013 ◽  
Vol 305 (6) ◽  
pp. H939-H945 ◽  
Author(s):  
Jennifer C. Irvine ◽  
Ravina M. Ravi ◽  
Barbara K. Kemp-Harper ◽  
Robert E. Widdop
Keyword(s):  
No Donor ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Angeli's Salt ◽  
Isolated Aorta ◽  
Vasodilatory Action ◽  
Wistar Kyoto ◽  
First Time

Nitroxyl (HNO), the redox congener of nitric oxide, has numerous vasoprotective actions including an ability to induce vasodilation and inhibit platelet aggregation. Given HNO is resistant to scavenging by superoxide and does not develop tolerance, we hypothesised that HNO would retain its in vivo vasodilatory action in the setting of hypertension. The in vitro and in vivo vasodilator properties of the HNO donors Angeli's salt (AS) and isopropylamine/NONOate (IPA/NO) were compared with the NO˙ donor diethylamine/NONOate (DEA/NO) in spontaneously hypertensive rats (SHR) and normotensive [Wistar-Kyoto (WKY) rats]. AS (10, 50, and 200 μg/kg), IPA/NO (10, 50, and 200 μg/kg), and DEA/NO (1, 5, and 20 μg/kg) caused dose-dependent depressor responses in conscious WKY rats of similar magnitude. Depressor responses to AS and IPA/NO were significantly attenuated ( P < 0.01) after infusion of the HNO scavenger N-acetyl-l-cysteine (NAC), confirming that AS and IPA/NO function as HNO donors in vivo. In contrast, responses to DEA/NO were unchanged following NAC infusion. Depressor responses to AS and IPA/NO in conscious SHR retained their sensitivity to the inhibitory effects of NAC ( P < 0.01), yet those to DEA/NO in SHR were significantly ( P < 0.05) enhanced following NAC infusion. Importantly, depressor responses to AS, IPA/NO, and DEA/NO were preserved in hypertension and vasorelaxation to AS and DEA/NO, in isolated aorta, unchanged in SHR as compared with WKY rats. This study has shown for the first time that HNO donors exert antihypertensive effects in vivo and may, therefore, offer a therapeutic alternative to traditional nitrovasodilators in the treatment of cardiovascular disorders such as hypertension.

Neurons from neonatal hypertensive rats exhibit abnormal membrane properties in vitro

1990 ◽  
Vol 259 (3) ◽  
pp. C389-C396 ◽  
Author(s):  
B. C. Jubelin ◽  
M. S. Kannan
Keyword(s):  
Action Potentials ◽  
Membrane Properties ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Enzymatic Dissociation ◽  
Sd Rats ◽  
High Calcium ◽  
Cervical Ganglia ◽  
Wistar Kyoto

The in vitro membrane properties of neurons from superior cervical ganglia (SCG) of neonatal spontaneously hypertensive (SH), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were studied with microelectrodes. Neurons were obtained by enzymatic dissociation, plated, irradiated, and studied after 2-5 wk. Most SH neurons showed multiple action potentials in response to an intracellular long-duration depolarizing pulse (multiple firing), whereas most neurons from WKY or SD rats generated only one or two action potentials. Multiple firing was inhibited by low concentrations of cobalt (10(-5) M) but not by tetrodotoxin (TTX) (3 x 10(-6) M). Neither high calcium (5-10 x 10(-3) M) nor the Ca2+(-)channel opener BAY K 8644 (10(-6) M) could induce multiple firing in SD or WKY neurons. However, multiple firing was readily induced by apamin (10(-6) M) or tetraethylammonium chloride (5 x 10(-3) M) (Ca2+(-)activated K+(-)channels blockers), with cobalt and TTX sensitivities similar to native multiple-firing neurons. We conclude that 1) multiple firing is characteristic of neonate SH rats SCG neurons in vitro and depends on regenerative Ca2+ currents; 2) multiple firing in SH neurons results from a lack of activation of a Ca2+(-)activated K+ conductance and not from a lack of internal Ca2+ availability; and 3) multiple firing in SCG neurons mirrors a default in K+ conductance common to all cells in genetically hypertensive individuals.

Caspase Activation Is Required for Nitric Oxide–Mediated, CD95(APO-1/Fas)–Dependent and Independent Apoptosis in Human Neoplastic Lymphoid Cells

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4311-4320 ◽  
Author(s):  
Katerina Chlichlia ◽  
Marcus E. Peter ◽  
Marian Rocha ◽  
Carsten Scaffidi ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Present Report ◽  
Lymphoid Cells ◽  
Jurkat Cells ◽  
Target Cells ◽  
No Production ◽  
No Donor ◽  
Synthase Inhibitor ◽  
Inhibitor Of Protein Synthesis

Abstract Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant Jurkat subclone showed substantial protection from apoptosis after exposure to NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands. Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes which were also sensitive to anti-CD95 treatment. The ability of NO to induce apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1β converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8 activation. This activation was abrogated in some neoplastic lymphoid cells but not in others by the inhibitor of protein synthesis cycloheximide. Our results were confirmed using an in vitro experimental model of coculture of human lymphoid target cells with activated bovine endothelial cells generating NO as effectors. Furthermore, the inhibition of endogenous NO production with the inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete abrogation of the apoptotic effect. Our data provide evidence that NO-induced apoptosis in human neoplastic lymphoid cells strictly requires activation of caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending on the cell line tested this activation required or was independent of the CD95 receptor/ligand system.

Potassium channel-mediated vasorelaxation is impaired in experimental renal failure

1999 ◽  
Vol 277 (4) ◽  
pp. H1622-H1629 ◽  
Author(s):  
Jarkko Kalliovalkama ◽  
Pasi Jolma ◽  
Jari-Petteri Tolvanen ◽  
Mika Kähönen ◽  
Nina Hutri-Kähönen ◽  
...  
Keyword(s):  
Renal Failure ◽  
No Synthase ◽  
Sham Operation ◽  
No Donor ◽  
Plasma Urea ◽  
Failure Group ◽  
The Difference ◽  
Wistar Kyoto ◽  
Synthase Inhibitor ◽  
Experimental Renal Failure

Chronic renal failure is associated with increased cardiovascular morbidity and abnormal arterial tone, but the underlying pathophysiological mechanisms are poorly understood. Therefore, we studied the responses of isolated mesenteric arterial rings from Wistar-Kyoto rats in standard organ chambers 6 wk after subtotal (5/6) nephrectomy or sham operation. Subtotal nephrectomy resulted in a 1.7-fold elevation of plasma urea nitrogen, whereas blood pressure was not significantly affected. Endothelium-mediated relaxations of norepinephrine-precontracted rings to ACh were impaired in renal failure rats. The nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester inhibited relaxations to ACh more effectively in the renal failure group, whereas the cyclooxygenase inhibitor diclofenac did not significantly affect the response in either group. Inhibition of Ca2+-activated K+ channels by charybdotoxin and apamin attenuated NO synthase- and cyclooxygenase-resistant relaxations to ACh in control but not renal failure rats and abolished the difference between these groups. Endothelium-independent relaxations to isoproterenol and cromakalim, vasodilators acting via β-adrenoceptors and ATP-sensitive K+ channels, respectively, were impaired in the renal failure group, whereas relaxations to the NO donor nitroprusside were similar in both groups. In conclusion, endothelium-mediated relaxation in renal failure rats was impaired in the absence and presence of NO synthase and cyclooxygenase inhibition but not with prevented smooth muscle hyperpolarization. Endothelium-independent relaxations to isoproterenol and cromakalim were also attenuated after 5/6 nephrectomy. These results suggest that impaired vasodilatation in experimental renal failure could be attributed to reduced relaxation via arterial K+ channels.

Increased angiotensin II receptors in brain nuclei of DOCA-salt hypertensive rats

1988 ◽  
Vol 255 (3) ◽  
pp. H646-H650 ◽  
Author(s):  
J. S. Gutkind ◽  
M. Kurihara ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Area Postrema ◽  
Experimental Hypertension ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Salt Treatment ◽  
Brain Nuclei ◽  
Median Preoptic Nucleus ◽  
Wistar Kyoto

We analyzed angiotensin II (ANG II) receptors by in vitro autoradiography in selective brain nuclei of control, salt-treated (1% NaCl in drinking water), deoxycorticosterone acetate (DOCA)-treated (DOCA pivalate, 25 mg/kg sc weekly), and DOCA-salt-treated (DOCA + salt treatments) uninephrectomized male Wistar-Kyoto rats. After 4 wk of treatment, only the DOCA-salt group developed hypertension. ANG II binding increased in median preoptic nucleus and subfornical organ of salt- and DOCA-treated rats. DOCA-treated rats also showed increased ANG II binding in paraventricular nucleus. DOCA-salt-treated rats showed higher ANG II binding in nucleus of the solitary tract and area postrema, as well as in the areas mentioned before. Although salt and/or DOCA treatments alone increased ANG II receptors in some brain nuclei, after combined DOCA-salt treatment there was significantly higher ANG II binding in all areas, except the median preoptic nucleus. These results suggest that increased ANG II receptors in selected brain areas may play a role in the pathophysiology of mineralocorticoid-salt experimental hypertension.

Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion

1986 ◽  
Vol 250 (4) ◽  
pp. G412-G419
Author(s):  
H. P. Schedl ◽  
D. L. Miller ◽  
R. L. Horst ◽  
H. D. Wilson ◽  
K. Natarajan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Calcium Transport ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Depletion ◽  
Spontaneously Hypertensive ◽  
Distal Small Intestine ◽  
Wistar Kyoto

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.

In vitro diencephalic neuronal thermosensitivity in normotensive and hypertensive rats

1989 ◽  
Vol 256 (2) ◽  
pp. R560-R566
Author(s):  
K. A. Travis ◽  
J. A. Boulant
Keyword(s):  
Firing Rate ◽  
Spontaneous Activity ◽  
Tissue Temperature ◽  
Tissue Slices ◽  
Spontaneously Hypertensive ◽  
Dorsomedial Hypothalamus ◽  
Firing Rates ◽  
Wistar Kyoto ◽  
Morphological Differences

Because morphological differences exist in hypothalamic neurons from spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, the present study recorded neuronal spontaneous activity and thermosensitivity from diencephalic tissue slices of these two strains. With the use of extracellular recordings from horizontal tissue slices, neurons were characterized according to location, firing rate at 37 degrees C, and firing rate response to changes in local tissue temperature. Compared with WKY neurons, SH neurons had higher firing rates in the preoptic-anterior hypothalamus and lower firing rates in the dorsomedial hypothalamus. In addition, SH warm-sensitive neurons were less thermosensitive over the hyperthermic range (37-40 degrees C), and SH temperature-insensitive neurons had higher spontaneous firing rates. These differences in spontaneous activity and thermosensitivity provide a neuronal basis to explain the elevation of core temperature observed in SH rats.

Ca fluxes across duodenum and colon of spontaneously hypertensive rats: effect of 1,25(OH)2D3

1986 ◽  
Vol 251 (2) ◽  
pp. F278-F282 ◽  
Author(s):  
U. Gafter ◽  
S. Kathpalia ◽  
D. Zikos ◽  
K. Lau
Keyword(s):  
Calcium Transport ◽  
Spontaneously Hypertensive Rats ◽  
Calcium Absorption ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Calcium Flux ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Calcium absorption by spontaneously hypertensive rats (SHR) was variably reported to be different from normotensive Wistar-Kyoto (WKY) controls. Furthermore, blunted responsiveness to the intestinal effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has also been postulated. To evaluate this hypothesis, calcium fluxes were measured by the Ussing technique across duodenum and descending colon with or without prior 1,25(OH)2D3 treatment. Duodenal mucosal-to-serosal calcium flux (Jm----s) (44.9 vs. 52.4 nmol X cm-2 X h-1), serosal-to-mucosal flux (Js----m) (25.6 vs. 28.4 nmol X cm-2 X h-1), and net flux (Jnet) were comparable. 1,25(OH)2D3 increased duodenal Jm----s in both SHR and WKY groups (95.2 and 86.8 nmol X cm-2 X h-1). Js----m was lower in SHR (26.1 vs. 35.6 nmol X cm-2 X h-1, P less than 0.01), although the tendency for a higher Jnet in SHR (68.6 vs. 51.2 nmoles X cm-2 X h-1) was statistically insignificant. Short-circuit current was higher in the colon of SHR, both before and after 1,25(OH)2D3, suggesting increased sodium transport. Basal colonic Jnet was virtually zero in both groups but comparably increased by 1,25(OH)2D3 because of stimulation in only Jm----s. Prevention of hypertension by hydralazine since the 4th wk of age did not alter the findings compared with the hypertensive SHR, suggesting calcium transport rates were unaffected by hypertension. These data indicate that in vitro, duodenal, and colonic active calcium transport by the SHR is similar to WKY. Their normal responses to 1,25(OH)2D3 do not support the hypothesis of intestinal resistance.

Myogenic tone in mesenteric arteries from spontaneously hypertensive rats

1996 ◽  
Vol 270 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
A. S. Izzard ◽  
S. J. Bund ◽  
A. M. Heagerty
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Mesenteric Arteries ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tension Development ◽  
Spontaneously Hypertensive ◽  
Wide Pressure Range ◽  
Wistar Kyoto ◽  
Wide Pressure

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.

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