Search

The responsiveness of the basilar artery to intrinsic vasoactive substances is species-specific and can be a unique characteristic. We investigated the responsiveness of the bat (Rhinolophus ferrumequinum) basilar artery to noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin (Ang) II, bradykinin (BK), histamine (His), and acetylcholine (ACh). NA, 5-HT, Ang II, and BK induced contraction, whereas His and ACh induced relaxation, in a concentration-dependent manner. The NA cumulative concentration-response curve was shifted to the right in parallel with phentolamine (an α-antagonist). However, propranolol, a β-antagonist, had no significant effect. The 5-HT curve was shifted to the right in parallel by ketanserin (a 5-HT 2 antagonist) and methiothepin (a 5-HT 1 and 5-HT 2 antagonist). Losartan (an AT 1 antagonist) shifted the Ang II curve to the right, whereas PD123319 (an AT 2 antagonist) had no significant effect. L-NA, indomethacin, and des-Arg 9 -[Leu 8 ]-BK (a B 1 antagonist) did not significantly affect BK-induced contractions. HOE140 (a B 2 antagonist) shifted the BK concentration-response curve to the right. The His curve was shifted to the right weakly by diphenhydramine (an H 1 antagonist) and strongly by cimetidine (a H 2 antagonist). ACh-induced relaxation was significantly inhibited by L-NA, atropine, and pFHHSiD (a muscarinic M 3 antagonist), whereas pirenzepine and methoctramine (muscarinic M 1 and M 2 antagonists, respectively) showed no significant effects. At a resting vascular tone, L-NA-induced contraction and indomethacin induced relaxation. These results suggest that α-adrenergic, 5-HT 1 , 5-HT 2 , AT 1 , and B 2 receptors might be important in arterial contraction, whereas M 3 and H 2 (>H 1 ) receptors might modify these contractions, inducing relaxation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Diabetes mellitus comprises a heterogeneous group of metabolic disorders with underlying hyperglycemia and secondary cardiovascular complications. Growing evidence suggests that vascular dysfunction is among the most important causes of diabetic cardiovascular disease. Therefore, we determined whether streptozotocin (STZ)-induced diabetes in mice affects blood pressure and cerebral arterial responsiveness to angiotensin (Ang) II and acetylcholine (ACh), which are important modulators of cerebrovascular autoregulation. Diabetes was induced using a single intraperitoneal injection of STZ (50 mg/kg). Blood pressure was measured in conscious mice using the indirect tail-cuff method. Functional studies of the isolated arteries' response to vasoactive substances were performed using a micro-organ-bath system at 60 days after STZ injection. Systolic, diastolic, and mean blood pressures significantly increased at days 45 and 60 in the STZ-induced diabetic mice. In the isolated basilar arteries, ACh-induced relaxation, which is dependent on nitric oxide (NO) production from endothelial cells, decreased. In contrast, Ang II-induced contraction, mediated via rho-kinase activation in the smooth muscle, increased in the diabetic mice. There was significantly greater relaxation in the precontracted isolated basilar arteries of diabetic mice that had been treated with Y27632, a rho-kinase inhibitor, than in the control mice arteries. Pretreatment with Nω-nitro-L-arginine (L-NAME), an NO synthase inhibitor, significantly enhanced Ang II-induced contraction and Y27632-induced relaxation in the control basilar arteries but not in the STZ-induced diabetic mice arteries. These results suggest that decreased NO bioavailability and enhanced rho-kinase activity in basilar arteries contribute to altered reactivity to ACh and Ang II, respectively, in STZ-induced diabetic mice.

Aims: Methylmercury (MeHg) exposure results in increased risk of hypertension and cardiovascular diseases. In this study, we aimed to investigate whether the in vivo exposure of MeHg in mice affects blood pressure and basilar arterial responses to angiotensin II (Ang II) and acetylcholine (ACh), which are important modulators of cerebrovascular autoregulation., Main Methods: Mice were exposed to MeHg (40ppm) in drinking water for 21days. Blood pressure was measured in conscious mice by an indirect tail-cuff method. Functional studies of the isolated arteries' response to vasoactive substances were performed using a micro-organ-bath system., Key Findings: Systolic and mean blood pressures were significantly increased after 2 and 3weeks of treatment with MeHg, respectively. Ang II-induced contraction in an isolated basilar artery, which is mediated via Rho-kinase activation, was increased in MeHg-treated mice. ACh-induced relaxation, which is dependent on NO production from the endothelial cells, was decreased in MeHg-treated mice. However, alterations of vascular responses to Ang II and ACh were not observed in the isolated thoracic aorta., Significance: This study demonstrated that the cerebral vasculature appears to be particularly sensitive to in vivo exposure of MeHg. Our results suggest that in vivo MeHg increases blood pressure and causes alterations in the cerebrovascular reactivity in response to Ang II and ACh through enhancement of Rho-kinase activity and inhibition of NO bioavailability, respectively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Habu snakes (Protobothrops flavoviridis) are pit vipers found in the geographically adjacent but ecologically divergent islands of Tokunoshima and Amami-Oshima in southwestern Japan. Abiotic factors can cause variation in animal populations between the two islands, and Habu snakes may show such intraspecific physiological variation. We therefore evaluated the vasoreactivity in aortas isolated from the Habu of both islands. Tokunoshima Habu showed significantly greater contractile responses to angiotensin (Ang) II, acetylcholine (ACh) and noradrenaline, and significantly higher affinities (pEC50) for Ang II and ACh, than Amami-Oshima Habu. ACh caused contractions in aortas from both populations, a finding previously unreported in snakes. Our findings indicate that vasoreactivity may differ between Tokunoshima and Amami-Oshima Habu. [ABSTRACT FROM AUTHOR]

Simple Summary: Snakes are reptiles that have evolved over a period of approximately 170 million years, adapting to life in different habitats, including water (rivers and oceans), on the ground, in trees, and underground. The distance from the heart to the brain is known to be shorter in arboreal snakes compared to terrestrial ones, indicating that differences in habitat may also affect vascular response. In this study, we attempted to characterize vasoreactivity in the Tokara habu, a semi-arboreal snake. The Tokara habu snakes demonstrated a number of relaxation responses to various vasoactive substances, and they showed complex vasoreactivity, a contrast to the simple vasoreactivity seen in terrestrial snakes. These results suggest that the Tokara habu's distinctive, complex vasoreactivity may reflect adaptation to its semi-arboreal environment. Comparisons of vascular responses may be useful as a new approach to behavioral and ecological studies for species that are difficult to observe in the field. Vasoreactivity is relatively well documented in terrestrial snakes but has previously been investigated in only one semi-arboreal snake species. Consequently, the extent to which vasoreactivity is common across snake taxa or varies by habitat is unclear. The Tokara habu (Protobothrops tokarensis) is a semi-arboreal snake endemic to only two small adjacent Japanese islands, and hence a useful species for further investigation of vasoreactivity. We evaluated responses to known vasoactive substances in thoracic aortas isolated from Tokara habu. Under resting tension, noradrenaline and angiotensin II induced concentration-dependent contraction, but acetylcholine, serotonin (5-hydroxytriptamine; 5-HT), and isoproterenol induced relaxation followed by contraction. Histamine and rattlesnake bradykinin had no effect. Experiments with receptor-specific antagonists suggest that M1 and M3 receptors are involved in the acetylcholine-induced response; 5-HT1, 5-HT2, and 5-HT7 receptors in the serotonin-induced response; and β1 and β2 adrenoceptors in isoproterenol-induced relaxation. This is the first report on such response patterns in snakes (including serotonin- and isoproterenol-induced relaxation). Nitric oxide may be involved in acetylcholine-induced relaxation but not in the responses to serotonin or isoproterenol. In contrast to the uniform vasoreactivity observed in terrestrial snakes, the vasoreactivity of semi-arboreal snakes may be governed by diverse regulatory mechanisms. [ABSTRACT FROM AUTHOR]

From an evolutionary aspect, dolphins share a very close phylogenetic relationship with pigs. Previously, we characterized porcine cerebral artery responsiveness to intrinsic vasoactive substances. Therefore, here, we investigated dolphin (Tursiops truncatus) cerebral artery responsiveness to 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, acetylcholine (ACh), noradrenaline (NA), and bradykinin (BK) to characterize their related receptor subtypes. We also compared dolphin cerebral artery responsiveness with porcine cerebral artery responsiveness. We found that 5-HT and His induced concentration-dependent contraction of the dolphin cerebral artery. Ketanserin (a 5-HT2 antagonist) and methiothepin (a 5-HT1 and 5-HT2 antagonist) shifted the concentration-response curve for 5-HT to the right. Although diphenhydramine (an H1 antagonist) shifted the concentration-response curve for His to the right, cimetidine (an H2 antagonist) had no such effect. Ang II and ACh did not produce any vasomotor actions. NA induced concentration-dependent relaxation. Propranolol (a β antagonist) shifted the concentration-response curve for NA to the right, whereas phentolamine (an α antagonist) had no significant effect. BK induced relaxation followed by contraction in pre-contracted arteries with intact endothelium. HOE140 (a B2 antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg9-[Leu8]-BK (a B1 antagonist) had no significant effect. These results suggest that 5-HT1, 5-HT2, and H1 receptor subtypes are important in arterial contraction and that β and B2 receptor subtypes modify these contractions to relaxations. The responsiveness of the dolphin cerebral artery is very similar to that of porcine cerebral artery, supporting their evolutionary linkage. [ABSTRACT FROM AUTHOR]

Angiotensin (Ang) II is known to promote vascular disease and hypertension, partly through its effect on vascular endothelium. Bradykinin (BK) is an endothelium-dependent agonist that induces relaxation followed by contraction of the porcine basilar artery through release of NO and PGF 2α , respectively. In this study, we evaluated the effect of Ang II-induced hypertension on basilar artery responsiveness to BK in the Microminipig (MMPig). Ang II (200 ng/kg/min) or vehicle was infused into MMPigs for 14 days using an osmotic mini-pump and blood pressure was monitored regularly. The responsiveness of subsequently isolated basilar arteries was then measured using a micro organ bath system. MMPig basilar artery endothelial cells were cultured and stimulated with Ang II or vehicle for 48 h. Mean blood pressure was significantly ( P < 0.05; n = 5) higher in Ang II-infused MMPigs than in vehicle-infused MMPigs. In vitro, BK-induced endothelium-dependent dilation of isolated basilar artery specimens was abolished and BK-induced contraction was significantly increased (E max : 15.85 ± 2.42% and 56.54 ± 2.71% of 60 mM KCl in control and Ang II group respectively at 10 − 7 M concentration of BK; P < 0.01; n = 5) in Ang II-infused MMPigs. Ang II stimulation of the endothelial cells significantly decreased (54.15% at 24 h; P < 0.05; n = three independent experiment performed in triplicate) the amount of BK-elicited NO and increased (44.27% at 24 h; P < 0.05; n = three independent experiment performed in triplicate) the amount of BK-elicited PGF 2α . These results suggest that the decrease of NO and increase of PGF 2α production from endothelial cells are responsible for cerebrovascular dysfunction in hypertension, possibly causing cerebrovascular contraction and thus increasing the risk of brain infarction. [ABSTRACT FROM AUTHOR]