scholarly journals Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension

2021 ◽  
Vol 14 (11) ◽  
pp. 1120
Author(s):  
Marta Baranowska-Kuczko ◽  
Hanna Kozłowska ◽  
Monika Kloza ◽  
Magdalena Kusaczuk ◽  
Ewa Harasim-Symbor ◽  
...  
Keyword(s):  
Endocannabinoid System ◽  
Vessel Diameter ◽  
Secondary Hypertension ◽  
Hypertensive Rats ◽  
Independent Manner ◽  
Once Daily ◽  
Spontaneously Hypertensive ◽  
Calcium Activated Potassium Channels ◽  
Model Independent ◽  
Calcium Activated Potassium Channel

Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive rats (SHR). CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in response to acetylcholine in the aortas and G3 of DOCA-salt rats and SHR. The enhancement of vasorelaxation was prevented by the inhibition of nitric oxide (NO) with L-NAME and/or the inhibition of cyclooxygenase (COX) with indomethacin in the aortas and G3 of DOCA-salt and SHR, respectively. The mechanism of the CBD-mediated improvement of endothelial function in hypertensive vessels depends on the vessel diameter and may be associated with its NO-, the intermediate-conductance calcium-activated potassium channel- or NO-, COX-, the intermediate and the small-conductance calcium-activated potassium channels-dependent effect in aortas and G3, respectively. CBD increased the vascular expression of the cannabinoid CB1 and CB2 receptors and aortic levels of endocannabinoids with vasorelaxant properties e.g., anandamide, 2-arachidonoylglycerol and palmitoyl ethanolamide in aortas of DOCA-salt and/or SHR. In conclusion, CBD treatment has vasoprotective effects in hypertensive rats, in a vessel-size- and hypertension-model-independent manner, at least partly via inducing local vascular changes in the endocannabinoid system.

Cerebral artery responses to pressure and flow in uremic hypertensive and spontaneously hypertensive rats

2003 ◽  
Vol 284 (4) ◽  
pp. H1212-H1216 ◽  
Author(s):  
D. I. New ◽  
A. M. S. Chesser ◽  
R. C. Thuraisingham ◽  
M. M. Yaqoob
Keyword(s):  
Blood Flow ◽  
Cerebral Artery ◽  
Spontaneously Hypertensive Rats ◽  
Perfusion Pressure ◽  
Hypertensive Rats ◽  
Independent Manner ◽  
Spontaneously Hypertensive ◽  
Cerebral Blood Flow Autoregulation ◽  
Wistar Kyoto ◽  
Normotensive Control

Impaired cerebral blood flow autoregulation is seen in uremic hypertension, whereas in nonuremic hypertension autoregulation is shifted toward higher perfusion pressure. The cerebral artery constricts in response to a rise in either lumen pressure or flow; we examined these responses in isolated middle cerebral artery segments from uremic Wistar-Kyoto rats (WKYU), normotensive control rats (WKYC), and spontaneously hypertensive rats (SHR). Pressure-induced (myogenic) constriction developed at 100 mmHg; lumen flow was then increased in steps from 0 to 98 μl/min. Some vessels were studied after endothelium ablation. Myogenic constriction was significantly lower in WKYU (28 ± 2.9%) compared with both WKYC (39 ± 2.5%, P = 0.035) and SHR (40 ± 3.1%, P = 0.018). Flow caused constriction of arteries from all groups in an endothelium-independent manner. The response to flow was similar in WKYU and WKYC, whereas SHR displayed increased constriction compared with WKYU ( P < 0.001) and WKYC ( P < 0.001). We conclude that cerebral myogenic constriction is decreased in WKYU, whereas flow-induced constriction is enhanced in SHR.

CHARACTERISTIC OF AGE-DEPENDENT CHANGES IN PIAL ARTERIAL VESSELS ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

2020 ◽  
pp. 663-672
Author(s):  
О. П. Горшкова
Keyword(s):  
Small Diameter ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Synthesis System ◽  
Spontaneously Hypertensive ◽  
Small Vessels ◽  
Age Dependent ◽  
Calcium Activated Potassium Channels ◽  
Pial Arterial Vessels

Изучено изменение роли эндотелиальной гиперполяризации ( EDH ) в эндотелий-зависимой регуляции тонуса мозговых сосудов при старении в отсутствии и в условиях длительно текущей артериальной гипертензии (АГ). Исследовали роль EDH , индуцируемой активацией IK -каналов, и NO в дилатации пиальных артериальных сосудов на ацетилхолин у нормотензивных ( WKY ) и спонтанно гипертензивных крыс ( SHR ) в возрасте 4 и 18 мес. Установлено, что у крыс WKY механизм EDH преимущественно выражен в группе мелких сосудов. В процессе старения происходит снижение вклада EDH в осуществление дилатации мелких и средних сосудов с одновременным его повышением у артерий диаметром более 40 мкм. АГ приводит к повышению вклада процессов EDH в дилатацию сосудов мелкого и среднего диаметра. Старение, сопровождаемое длительно текущей АГ, снижает вклад EDH в дилатацию. У 18-месячных крыс SHR этот механизм выражен только в группе мелких сосудов диаметром менее 20 мкм. В основе возрастных изменений роли механизмов EDH в дилататорных ответах сосудов у крыс WKY и SHR лежит нарушение системы синтеза NO и изменение роли NO -опосредованных механизмов в эндотелийзависимой вазодилатации. A comparative study of changes in the contribution of endothelium-dependent hyperpolarization (EDH) induced by activation of the intermediate-conductance calcium-activated potassium channels ( IK ) channels and the contribution of NO in pial arterial vessels dilation to acetylcholine (ACh) in normotensive ( WKY ) and spontaneously hypertensive ( SHR ) rats at the age of 4 and 18 months was conducted. It was found that in WKY , the EDH is mainly expressed in the group of small pial arterial vessels. During aging, the contribution of EDH to the dilatation of small (diameter less than 20 microns) and medium (20-40 microns) vessels decreases, while it increases in arteries with a diameter of more than 40 microns. Hypertension (HT) leads to an increase in the contribution of EDH processes to dilation of vessels of small and medium diameters. Aging, accompanied by long-term HT, reduces the contribution of EDH to dilation. In 18-month-old SHR, this mechanism is expressed only in a group of small vessels. Age-dependent changes in the EDH contribution in pial arterial vessels dilation in WKY and SHR rats are based on the NO synthesis system damage and a change in the NO -mediated contribution in endothelium-dependent vasodilation.

Venule distension properties in Wistar, Wistar-Kyoto, and spontaneously hypertensive rats

1987 ◽  
Vol 252 (4) ◽  
pp. H714-H720
Author(s):  
D. J. Lang ◽  
B. L. Johns
Keyword(s):  
Vessel Wall ◽  
Wistar Rats ◽  
Spontaneously Hypertensive Rat ◽  
Venous Pressure ◽  
Vessel Diameter ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
First Order ◽  
Disease Mechanisms ◽  
Wistar Kyoto

The purpose of this study was to determine whether venule distension characteristics are modified in denervated venules in the spontaneously hypertensive rat (SHR) during the developmental stage of hypertension. The distension of denervated first-order venules (1V) and small collecting veins (SCV) in the intestine of 7- to 8-wk-old SHR, Wistar-Kyoto (WKY), and Wistar rats were measured with intravital microscopy during venous pressure elevation. Diameter strain and distensibility were calculated for the 1V and SCV from vessel diameter and servo-null pressure. The Wistar 1V underwent larger strains and distensibilities than the WKY or SHR vessels, which had similar characteristics. For the SCV, the Wistar and WKY strains and distensibilities were similar, with the SHR different from these at only certain pressure elevations. Thus no consistent patterns of altered distension characteristics were found in denervated SHR SCV or 1V compared with its controls. This study does not distinguish between changes in local active and passive factors in the vessel wall which may influence distension. Our results may be consistent with disease mechanisms in the 7- to 8-wk-old SHR which leave these local factors unchanged or with mechanisms which have local venular effects that counterbalance each other, leaving the distension behavior of the denervated venules unchanged.

Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent manner

2002 ◽  
Vol 103 (s2002) ◽  
pp. 385S-388S ◽  
Author(s):  
Jörg TRENKNER ◽  
Friedrich PRIEM ◽  
Christian BAUER ◽  
Hans-Hellmut NEUMAYER ◽  
Manfred RASCHAK ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Hypertensive Rats ◽  
Independent Manner ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Protein Excretion ◽  
Pressure Independent

The renal endothelin (ET) system is involved in the pathogenesis of kidney fibrosis as well as blood pressure control by regulating tubular sodium excretion. Long-term effects of ETA receptor blockade on blood pressure and kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than for ETB) with 10, 30 and 100mg·kg-1·day-1 or placebo. The ETA antagonist had at no time-point any effect on blood pressure. Glomerular filtration rate was normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion was markedly reduced by the ETA antagonist (SHR-S, 145±50mg/day; SHR-S+10mg·kg-1·day-1 LU 135252, 33±11mg/day, P<0.05 versus SHR-S; SHR-S+30mg·kg-1·day-1 LU 135252, 55±16mg/day and SHR-S+100mg·kg-1·day-1 LU 135252, 32±11mg/day, P<0.05 versus SHR-S at both concentrations). Total urinary protein excretion was likewise significantly reduced by treatment with 10mg·kg-1·day-1 LU 135252 (SHR-S, 0.25±0.06g/day; SHR-S+10mg·kg-1·day-1 LU 135252, 0.089±0.01g/day, P<0.05 versus SHR-S). The higher dosages of LU 135252 showed only a trend towards reduction of total urinary protein excretion. Computer-aided image analysis after haematoxylin/eosin and periodic acid-Schiff staining revealed that treatment with 10mg·kg-1·day-1 LU 135252 significantly reduces the media/lumen ratio of intrarenal arteries. Higher dosages of LU 135252 were less effective. Renal matrix protein synthesis in SHR-S was not altered by LU 135252. In conclusion, the renal ET system contributes in a blood-pressure-independent manner to the regulation of urinary protein excretion and renal vascular hypertrophy in SHR-S. Lower doses of the ETA antagonist were more effective, indicating that a potential additional blockade of the ETB receptor using higher doses of LU 135252 seems to oppose the beneficial effects of a sole ETA blockade. Urinary protein excretion is an independent risk factor of chronic renal failure, thus ETA antagonists might be a therapeutic tool to prevent proteinuria-induced chronic renal failure.

Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats

2018 ◽  
Vol 96 (8) ◽  
pp. 839-844
Author(s):  
Makoto Ando ◽  
Takayuki Matsumoto ◽  
Shota Kobayashi ◽  
Maika Iguchi ◽  
Kumiko Taguchi ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Combined Treatment ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Α Subunit ◽  
Spontaneously Hypertensive ◽  
The Difference ◽  
Wistar Kyoto ◽  
Calcium Activated Potassium Channel ◽  
Relationship Of

The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca2+-activated K+ channels (BKCa) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.

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