Effect of diabetes on vascular smooth muscle function in normotensive and spontaneously hypertensive rat mesenteric artery

1987 ◽  
Vol 65 (11) ◽  
pp. 2274-2280 ◽  
Author(s):  
D. K. Agrawal ◽  
J. H. McNeill
Keyword(s):  
Mesenteric Artery ◽  
Spontaneously Hypertensive Rat ◽  
Functional Responses ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Rat Mesenteric Artery ◽  
Significant Difference ◽  
Adrenoceptor Agonists ◽  
Wistar Kyoto ◽  
The Right

We have examined the functional responses to α-adrenoceptor agonists (α1-selective: methoxamirte and phenylephrine; α2-selective: clonidine and B-HT 920; non-selective: norepinephrine, serotonin and K+ in ring segments of mesenteric artery of control and streptozotocin-induced diabetic spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Systolic blood pressure and contractile responses were examined after 12 weeks of diabetes. There was no significant change in the diabetic WKY rats as compared with the control WKY rats. However, diabetic SHR had significantly less hypertension than control SHR. Responses to serotonin and α2-adrenoceptor agonists were augmented significantly in arteries from control SHR animals as compared with vessels from WKY animals. There was no significant difference in the force of contraction generated by other agonists in both nondiabetic groups. Responses to all agonists in WKY diabetic and to methoxamine and K+ in SHR diabetic arteries were increased as compared with their respective controls. ED50 values for each agonist were similar in all groups. Indomethacin (5 μM) shifted the dose–response curve to norepinephrine to the right in arteries from all groups of animals. However, in the diabetic SHR and WKY, there was a significant reduction in norepinephrine maximum response. Nifedipine was more potent in inhibiting the contraction to K+ and serotonin in WKY diabetic arteries as compared with WKY controls. However, nifedipine inhibited the responses to all agonists with equal potency in the control and diabetic SHR vessels. These results suggest the involvement of α2-adrenoceptors and serotonin receptors in the development and (or) the maintenance of hypertension. Furthermore, the hyperresponsiveness of the diabetic vessels could be due to an alteration in the postreceptor excitation–contraction coupling, possibly involving prostaglandin and an increased activity of calcium channels.

Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery

1993 ◽  
Vol 265 (2) ◽  
pp. H509-H516 ◽  
Author(s):  
K. Fujii ◽  
S. Ohmori ◽  
M. Tominaga ◽  
I. Abe ◽  
Y. Takata ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
K Channel ◽  
Aged Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Age Related ◽  
Rat Mesenteric Artery ◽  
Wistar Kyoto ◽  
Age Related Changes

This study was designed to determine the age-related changes in the endothelium-dependent hyperpolarization to acetylcholine (ACh) and its contribution to relaxation in the isolated mesenteric artery from normotensive and hypertensive rats. Membrane potentials and contractions were recorded in arteries from male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) that were 5-6 wk old (young), 6-8 mo old (adult), and 20-26 mo old (aged). Endothelium-dependent hyperpolarizations produced by ACh, applied both at the resting state of the membrane and under conditions of depolarization with norepinephrine (10(-5) M), were markedly impaired in aged WKY rats, adult SHR, and aged SHR. Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were also impaired in aged WKY rats, adult SHR, and aged SHR even in the presence of indomethacin. Furthermore, in these rats, N omega-nitro-L-arginine, an inhibitor of nitric oxide formation, showed potent inhibitory effects on the relaxations, whereas the 20 mM high K+ solution that reduces hyperpolarization had less pronounced effects. Hyperpolarizations and relaxations to cromakalim (10(-5) M), a K(+)-channel opener, were on the whole preserved in aged rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced with aging as well as by hypertension, and this would, in part, account for the impaired relaxation to ACh in arteries of both aged rats and hypertensive rats.

Endothelin-1 and -3 cause endothelium-dependent hyperpolarization in the rat mesenteric artery

1993 ◽  
Vol 265 (6) ◽  
pp. H2137-H2141 ◽  
Author(s):  
M. Nakashima ◽  
P. M. Vanhoutte
Keyword(s):  
Mesenteric Artery ◽  
Mesenteric Arteries ◽  
Receptor Subtype ◽  
Spontaneously Hypertensive ◽  
Rat Mesenteric Artery ◽  
Significant Difference ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Wistar Kyoto ◽  
Eta Receptor Antagonist

The present study was designed to determine whether endothelin (ET) induces endothelium-dependent hyperpolarization in the isolated rat mesenteric artery and, if so, to identify the receptor subtype involved. Main superior mesenteric arteries of Wistar-Kyoto and spontaneously hypertensive rats were used for the measurement of electrical responses of smooth muscle cells, using glass microelectrode. In tissues with endothelium of both strains, ET-1 (10(-8) M) caused an initial transient hyperpolarization followed by a sustained depolarization. In tissues without endothelium, only depolarization was observed. ET-3 (10(-8) M) produced transient hyperpolarizations only in preparations with endothelium. There was no significant difference in maximal amplitude of hyperpolarization between the two strains. BQ-123 (selective ETA-receptor antagonist) blocked the depolarization to ET-1 but did not inhibit hyperpolarizing responses to either isopeptide. IRL-1620 (specific ETB-receptor agonist) produced transient membrane hyperpolarizations in tissues with endothelium. The hyperpolarizations induced by ET were not affected by NG-nitro-L-arginine. These data suggest that both ET-1 and ET-3 can cause endothelium-dependent hyperpolarization in the rat mesenteric artery and that the endothelial receptor involved may belong to ETB subtype.

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rat ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urotensin Ii ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Hypertensive Rat ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

1985 ◽  
Vol 63 (10) ◽  
pp. 1258-1262 ◽  
Author(s):  
Corey B. Toal ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Response ◽  
Receptor Occupancy ◽  
Pressure Response ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Freely Moving ◽  
Wistar Kyoto

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p < 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact consious SHR at 16 weeks of age.

scholarly journals Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat

2013 ◽  
Vol 305 (7) ◽  
pp. H980-H986 ◽  
Author(s):  
Julia Shanks ◽  
Sotiria Manou-Stathopoulou ◽  
Chieh-Ju Lu ◽  
Dan Li ◽  
David J. Paterson ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Calcium Transients ◽  
Vagus Stimulation ◽  
Spontaneously Hypertensive ◽  
Sympathetic Dysfunction ◽  
The Difference ◽  
Wistar Kyoto ◽  
The Right ◽  
Right Atria

Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant ( P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs ( n = 19) compared with WKYs ( n = 16) but not in response to exogenous NE (0.025–5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [3H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [3H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.

scholarly journals Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246254
Author(s):  
Lucía Isidoro-García ◽  
Diva M. Villalpando ◽  
Mercedes Ferrer
Keyword(s):  
Mesenteric Artery ◽  
Electrical Field Stimulation ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Vasomotor Function ◽  
Wistar Kyoto ◽  
And Function

Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5β-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5β-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5β-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5β-DHT previously described in conscious SHR and WKY rats, pointing to 5β- DHT as a potential drug for the treatment of hypertension.

scholarly journals Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.

1994 ◽  
Vol 5 (4) ◽  
pp. 1125-1132
Author(s):  
A Debska-Slizien ◽  
P Ho ◽  
R Drangova ◽  
A D Baines
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Membrane Vesicle ◽  
Proximal Tubules ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Endogenous Dopamine ◽  
Hypertensive Rat ◽  
Wistar Kyoto ◽  
Signaling Process ◽  
Rat Kidneys

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals ACE Inhibition Reduces Infarction in Normotensive but Not Hypertensive Rats: Correlation with Cortical ACE Activity

2010 ◽  
Vol 30 (8) ◽  
pp. 1520-1526 ◽  
Author(s):  
Michelle J Porritt ◽  
Michelle Chen ◽  
Sarah SJ Rewell ◽  
Rachael G Dean ◽  
Louise M Burrell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Infarct Volume ◽  
Ace Inhibition ◽  
Artery Occlusion ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Wky Rats ◽  
Ace Activity ◽  
Wistar Kyoto

Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR.

scholarly journals Lack of Endogenous Adenosine Tonus on Sympathetic Neurotransmission in Spontaneously Hypertensive Rat Mesenteric Artery

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105540 ◽  
Author(s):  
Joana Beatriz Sousa ◽  
Maria Sofia Vieira-Rocha ◽  
Carlos Sá ◽  
Fátima Ferreirinha ◽  
Paulo Correia-de-Sá ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Sympathetic Neurotransmission ◽  
Endogenous Adenosine ◽  
Hypertensive Rat ◽  
Rat Mesenteric Artery

Dopamine and diltiazem-induced natriuresis in the spontaneously hypertensive rat

1997 ◽  
Vol 273 (1) ◽  
pp. R317-R323
Author(s):  
G. M. Eisner ◽  
L. D. Asico ◽  
F. E. Albrecht ◽  
P. A. Jose
Keyword(s):  
Calcium Channel ◽  
Spontaneously Hypertensive Rat ◽  
Great Part ◽  
Renal Medulla ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Channel Blockers ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto

An attenuated natriuretic response to dopamine and D1 agonists in genetic hypertension has been attributed to an uncoupling of the renal D1 dopamine receptor from its G protein-effector protein complex. We have reported that in normotensive Wistar-Kyoto (WKY) rats the natriuresis induced by calcium channel blockers is caused in part by activation of renal D1 dopamine receptors. We tested the interaction between the renal D1 receptor and a calcium channel blocker, diltiazem, infused into a renal artery of anesthetized spontaneously hypertensive rats (SHR) acutely loaded with 5% saline. Diltiazem produced a 50% increase in renal blood flow and nearly tripled absolute and fractional sodium excretion; urine flow rate more than doubled, but glomerular filtration rate did not change. However, the D1 receptor antagonist SKF-83742, which had no effect by itself, did not diminish the response to diltiazem. In a separate group of concurrent experiments, we found that the diltiazem-induced natriuresis was associated with a decrease in Na(+)-K(+)-adenosinetriphosphatase activity in the renal medulla of SHR. In contrast, in WKY rats, no changes were noted in the renal medulla but a decrease in Na(+)-K(+)-adenosinetriphosphatase activity was noted in the renal cortex. Diltiazem had no effect on urinary dopamine excretion in either rat strain. We conclude that diltiazem induces natriuresis differently in SHR and WKY rats; it is independent of D1 receptors in SHR and is in great part mediated by renal hemodynamic, rather than by cortical tubular, effects. These studies support previous findings of a defective renal cortical tubular D1 mechanism in SHR.

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