Changes in vascular function in hypertension: role of chloride in altered electromechanical coupling in salt hypertension
Year: 2004
Type: dissertation
Abstract: According to the working hypothesis put forth, the role of Cl-in excitationcontraction coupling is altered in salt hypertension, in part, due to altered nitric oxide (NO)/NO synthase pathways.To test this hypothesis, an assessment was made of the hemodynamic, mechanical, electrical and morphological properties in mesenteric blood vessels from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats.Female Dahl salt-resistant and salt-sensitive rats were placed on a 4% salt diet for 7 weeks.The Dahl SSH rats had significantly higher blood pressure, heart rate, I and body weight compared to SRN.In addition, the SSH rats had left ventricular and renal hypertrophy, but the plasma and total blood volume were not different compared to SRN.Morphological examination revealed an increase in media thickness and lumen diameter in mesenteric arteries from SSH, but the ratio of the two was not different between the strains.The a 1 -adrenoceptor agonist, cirazoline, produced a dose-dependent increase in blood pressure, decrease in heart rate, mesenteric blood flow, and mesenteric vascular conductance in anesthetized SRN and SSH rats.The nitric oxide synthase inhibitor Nw nitro-L-arginine methyl ester (L-NAME) increased blood pressure, decreased mesenteric blood flow and conductance in SRN but not in SSH.Niflumic acid-induced attenuation of cirazoline-mediated decreases in mesenteric blood flow and conductance was more pronounced in SRN than in SSH rats.This difference in the inhibitory actions of niflumic acid was abolished by pretreatment with L-NAME.-ii-In isolated perfused mesenteric blood vessels, replacement of Cl-with propionate ions significantly inhibited cirazoline-mediated vasoconstriction in SRN but not in SSH.Exposure to L-NAME potentiated cirazoline-induced vasoconstriction in SRN but not in SSH rats.The absence of Cl-significantly inhibited the potentiating effect ofL-NAME at the higher doses of cirazoline in SRN without any effects in SSH.The presence of niflumic acid significantly inhibited cirazoline-mediated vasoconstriction, the inhibition being more pronounced'in SRN than SSH.Niflumic acid did not produce any additional inhibitory effect in Cl--free medium.The resting Em of smooth muscle cells in superior mesenteric artery was not different I in SRN and SSH.Cirazoline did not produce a membrane depolarization in smooth muscle cells from either strain.Removal of Cl-from the extracellular space produced a significant depolarization which was significantly larger in SSH than SRN.Addition of L-NAME in normal Krebs resulted in significant depolarization in tissues from SRN but not in SSH.There was a lack of increased reactivity and magnitude in vasoconstrictor response to cirazoline in mesenteric blood vessels in SSH.The absence of increased reactivity in blood vessels from SSH can be attributed to receptor desensitization, morphology, and resting E 111 • Cl-handling and Ca 2 + -dependent Cl channel activity seem to undergo modification as a consequence of salt-induced hypertension.The dysfunction of the NO system and Cl-channels could contribute to the hypertension observed in the SSH model.-iii-ACKNOWLEDMENTS I am deeply indebted to my mentor, Dr. Reza Tabrizchi, for providing me with the opportunity to work on this project, for his guidance and advice, for his encouragement and support on numerous occasions without which this project would have been difficult to complete.I would
Author: Kakoli Parai
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2193656370