-
Science China. Life Sciences Jul 2014Autoimmune activities have been implicated in the pathogenesis of hypertension. High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor...
Autoimmune activities have been implicated in the pathogenesis of hypertension. High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor (α1-AR autoantibody, α1-AA) are found in patients with hypertension, and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect. However, whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown. Using aortic rings of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, we observed the vasoconstrictive responses to α1-AA with phenylephrine (α1-AR agonist) as a positive control drug. Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry. The results showed that the aortic constrictive responses to α1-AA and phenylephrine (both 1 nmol L(-1)-10 μmol L(-1)) were greater in SHR than in WKY rats. Endothelial denudation or L-NAME (a non-selective NOS inhibitor) (100 μmol L(-1)) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY. However, selective iNOS inhibitor 1400 W (10 μmol L(-1)) enhanced the α1-AA-induced aortic constriction in WKY, but not in SHR. The aortic nitrotyrosine level was significantly higher in SHR than WKY, as shown by both ELISA and immunohistochemistry. These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR, and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability. The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.
Topics: Adrenergic alpha-1 Receptor Agonists; Animals; Aorta; Autoantibodies; Blotting, Western; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Humans; Hypertension; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phenylephrine; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Receptors, Adrenergic, alpha-1; Tyrosine; Vasoconstriction; Vasoconstrictor Agents
PubMed: 24950619
DOI: 10.1007/s11427-014-4672-8 -
Journal of the American College of... Sep 1993
Comparative Study
Topics: Coronary Vessels; Humans; Nicotine; Risk Factors; Smoking; Vasoconstriction
PubMed: 8354793
DOI: 10.1016/0735-1097(93)90171-v -
Life Sciences Feb 2019Rilmenidine and moxonidine are centrally acting antihypertensive agents that are more selective for I-imidazoline receptors than for α-adrenergic receptors. Moxonidine...
AIMS
Rilmenidine and moxonidine are centrally acting antihypertensive agents that are more selective for I-imidazoline receptors than for α-adrenergic receptors. Moxonidine previously showed a peripheral vasoconstrictive effect stronger than generally recognized, which counteracted an arterial pressure (AP) lowering effect resulting from central sympathoinhibition. We tested whether rilmenidine also showed a significant vasoconstrictive effect that could attenuate its AP lowering effect.
MAIN METHODS
Efferent sympathetic nerve activity (SNA) and AP responses to changes in carotid sinus pressure were compared in nine anesthetized Wistar-Kyoto rats before and after low, medium, and high doses (40, 100, and 250 μg/kg, respectively) of intravenous rilmenidine.
KEY FINDINGS
High-dose rilmenidine narrowed the range of the SNA response (from 89.6 ± 2.9% to 50.4 ± 7.9%, P < 0.001) and reduced the lower asymptote of SNA (from 13.5 ± 3.0% to 2.7 ± 1.5%, P < 0.001). High-dose rilmenidine significantly increased the intercept (from 57.1 ± 3.8 to 78.2 ± 2.7 mm Hg, P < 0.001) but reduced the slope (from 0.82 ± 0.08 to 0.51 ± 0.07 mm Hg/%, P < 0.001) of the SNA-AP relationship. The reduction in the operating-point AP induced by high-dose rilmenidine did not significantly differ based on whether the peripheral effect was considered (-19.8 ± 2.2 vs. -26.4 ± 5.3 mm Hg, not significant).
SIGNIFICANCE
Rilmenidine increased AP in the absence of SNA, which suggests a peripheral vasoconstrictive effect; however, the vasoconstrictive effect was weak and did not significantly counteract the AP-lowering effect through central sympathoinhibition.
Topics: Animals; Antihypertensive Agents; Baroreflex; Blood Pressure; Carotid Sinus; Male; Rats; Rats, Inbred WKY; Rilmenidine; Sympathetic Nervous System; Vasoconstriction
PubMed: 30630007
DOI: 10.1016/j.lfs.2019.01.009 -
Transactions of the American Clinical... 2017Cirrhosis leads to portal hypertension and vascular abnormalities in multiple vascular beds. There is intense vasoconstriction in the liver and the kidneys, but also... (Review)
Review
Cirrhosis leads to portal hypertension and vascular abnormalities in multiple vascular beds. There is intense vasoconstriction in the liver and the kidneys, but also vasodilation in the other vascular beds, including the periphery, lungs, brain, and mesentery. The derangement in each of these beds leads to specific clinical disease. The vasoconstrictive phenotype in the liver ultimately leads to clinical portal hypertension, and is caused by an imbalance of vasoconstrictive and vasorelaxing molecules, which will be the focus of this review.
Topics: Animals; Endothelial Cells; Gene Expression Regulation; Hepatic Stellate Cells; Humans; Hypertension, Portal; Liver Cirrhosis; Vasoconstriction; Vasodilation
PubMed: 28790516
DOI: No ID Found -
American Journal of Physiology. Heart... Jan 2017Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest....
UNLABELLED
Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/dt, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN.
NEW & NOTEWORTHY
We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Arterial Pressure; Cardiac Output; Coronary Circulation; Coronary Vessels; Dogs; Female; Hindlimb; Hypertension; Hypertension, Renovascular; Muscle, Skeletal; Physical Conditioning, Animal; Prazosin; Reflex; Sympathetic Nervous System; Vasoconstriction; Ventricular Function
PubMed: 27769997
DOI: 10.1152/ajpheart.00417.2016 -
Pharmacogenetics and Genomics May 2005Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted...
OBJECTIVES
Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes.
METHODS
We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables.
RESULTS
Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion.
CONCLUSIONS
The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.
Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adult; Aged; Blood Pressure; Dexmedetomidine; Female; Heart Rate; Humans; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, alpha-2; Vasoconstriction
PubMed: 15864138
DOI: 10.1097/01213011-200505000-00012 -
The American Journal of Tropical... Feb 2018Cerebral malaria is a severe complication of falciparum malaria that occurs infrequently in adults. Here, we describe the case of a 21-year-old man who presented with...
Cerebral malaria is a severe complication of falciparum malaria that occurs infrequently in adults. Here, we describe the case of a 21-year-old man who presented with fever and headache 13 days after returning from a 12-day trip to Kenya and was subsequently diagnosed with falciparum malaria. Complications of cerebral malaria developed within 1 day after the initiation of therapy with intravenous quinine, and the patient entered a deep coma. Magnetic resonance angiography (MRA) revealed multiple vasoconstrictions in his brain. The resulting neurocognitive disorders that persisted after parasite clearance improved gradually, as confirmed by MRA, enabling the patient to perform activities of daily living upon discharge. In this case of cerebral malaria, the MRA findings indicated the involvement of reversible cerebral vasoconstriction syndrome.
Topics: Antimalarials; Fever; Humans; Magnetic Resonance Angiography; Malaria, Cerebral; Male; Pain; Quinine; Vasoconstriction; Young Adult
PubMed: 29260652
DOI: 10.4269/ajtmh.17-0665 -
Journal of Vascular Research 2019Ca2+ plays an important role in the regulation of vasoconstriction. Ca2+ signaling is regulated by a number of Ca2+-handling proteins. However, whether differences in... (Comparative Study)
Comparative Study
BACKGROUND
Ca2+ plays an important role in the regulation of vasoconstriction. Ca2+ signaling is regulated by a number of Ca2+-handling proteins. However, whether differences in Ca2+ handling affect the regulation of vasoconstriction in different arteries remains elusive.
OBJECTIVE
To determine whether differences in Ca2+ handling affect the response to vasoconstrictors in different arteries.
METHODS
Arterial ring contraction was measured using a Multi Myograph System. Vascular smooth muscle cells (VSMCs) were digested with type 2 collagenase in DMEM, then intracellular calcium concentration was measured with the Ca2+ probe fluo-4/AM in the isolated cells. Calcium-related proteins were assayed by Western blotting.
RESULTS
Phenylephrine did not induce -coronary arterial contraction. There were differences in -5-hydroxytryptamine, 9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F2a, and endothelin 1-induced vasoconstriction in different solutions between coronary and renal arteries. Vasoconstrictions in the presence of Bay K8644 were stronger in coronary than in renal arteries. Store-operated calcium (SOC) channels could mediate Ca2+ influx in VSMCs of both groups. SOC channels did not participate in the contraction of coronary arteries. In addition, there were significant differences in the expressions of receptors and ion channels between the two groups.
CONCLUSIONS
Ca2+ handling contributed to the different responses to vasoconstrictors between coronary and renal arteries.
Topics: Animals; Calcium; Calcium Signaling; Coronary Vessels; In Vitro Techniques; Male; Rats, Wistar; Renal Artery; Vasoconstriction; Vasoconstrictor Agents
PubMed: 31390638
DOI: 10.1159/000501614 -
Anesthesiology Aug 1996Although forced-air warming rapidly increases intraoperative core temperatures, it is reportedly ineffective postoperatively. A major difference between these two... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Although forced-air warming rapidly increases intraoperative core temperatures, it is reportedly ineffective postoperatively. A major difference between these two periods is that arteriovenous shunts are usually dilated during surgery, whereas vasoconstriction is uniform in hypothermic postoperative patients. Vasoconstriction may decrease efficacy of warming because its major physiologic purposes are to reduce cutaneous heat transfer and restrict heat transfer between the two thermal compartments. Accordingly, we tested the hypothesis that thermoregulatory vasoconstriction decreases cutaneous transfer of applied heat and restricts peripheral-to-core flow of heat, thereby delaying and reducing the increase in core temperature.
METHODS
Eight healthy male volunteers anesthetized with propofol and isoflurane were studied. Volunteers were allowed to cool passively until core temperature reached 33 degrees C. On one randomly assigned day, the isoflurane concentration was reduced, to provoke thermoregulatory arteriovenous shunt vasoconstriction; on the other study day, a sufficient amount of isoflurane was administered to prevent vasoconstriction. On each day, forced-air warming was then applied for 2 h. Peripheral (arm and leg) tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. Core (trunk and head) heat content was determined from core temperature, assuming a uniform compartmental distribution. Time-dependent changes in peripheral and core tissue heat contents were evaluated using linear regression. Differences between the vasoconstriction and vasodilation study days, and between the peripheral and core compartments, were evaluated using two-tailed, paired t tests. Data are presented as means +/-SD; P < 0.01 was considered statistically significant.
RESULTS
Cutaneous heat transfer was similar during vasoconstriction and vasodilation. Forced-air warming increased peripheral tissue heat content comparably when the volunteers were vasodilated and vasoconstricted: 48 +/- 7 versus 53 +/- 10 kcal/h. Core compartment tissue heat content increased similarly when the volunteers were vasodilated and vasoconstricted: 51 +/- 8 versus 44 +/- 11 kcal/h. Combining the two study days, the increase in peripheral and core heat contents did not differ significantly: 51 +/- 8 versus 48 +/- 10 kcal/h, respectively. Core temperature increased at essentially the same rate when the volunteers remained vasodilated (1.3 degrees C/h) as when they were vasoconstricted (1.2 degrees C/h).
CONCLUSIONS
The authors failed to confirm their hypothesis that thermoregulatory vasoconstriction decreases cutaneous transfer of applied heat and restricts peripheral-to-core flow of heat in anesthetized subjects. The reported difference between intraoperative and postoperative rewarming efficacy may result from nonthermoregulatory anesthetic-induced vasodilation.
Topics: Adult; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Body Temperature Regulation; Carbon Dioxide; Humans; Hyperthermia, Induced; Isoflurane; Male; Partial Pressure; Propofol; Skin; Skin Physiological Phenomena; Tidal Volume; Vasoconstriction
PubMed: 8712443
DOI: 10.1097/00000542-199608000-00009 -
Cells May 2024Norbormide (NRB) is a -selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to... (Review)
Review
Norbormide (NRB) is a -selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non- species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs' lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB's mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular K channels, which potentially controls its -selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable -selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications.
Topics: Animals; Rats; Rodenticides; Humans; Vasoconstriction; Mitochondrial Permeability Transition Pore
PubMed: 38727324
DOI: 10.3390/cells13090788