Different mechanism of LPS‐induced vasodilation in resistance and conductance arteries from SHR and normotensive rats

• Published in: British journal of pharmacology Vol. 137; no. 2; pp. 213 - 220
• Main Authors: Farias, Nelson C, Borelli‐Montigny, Gisele L, Fauaz, Grasiele, Feres, Teresa, Borges, Antonio C R, Paiva, Therezinha B
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2002; Nature Publishing
• Subjects: Animals; aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Arterial hypertension. Arterial hypotension; Arteries - drug effects; Arteries - physiology; Biological and medical sciences; Blood and lymphatic vessels; calcium‐dependent potassium channel; Cardiology. Vascular system; Dose-Response Relationship, Drug; endothelin; endotoxin; Experimental diseases; Hypertension - physiopathology; iberiotoxin; In Vitro Techniques; Lipopolysaccharides - pharmacology; LPS; Male; Medical sciences; membrane potential; Membrane Potentials - drug effects; mesenteric arteries; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Nitric Oxide - physiology; Nitroarginine - pharmacology; Peptides - pharmacology; Potassium Channels - physiology; rat vascular mesenteric bed; Rats; Rats, Inbred SHR; Rats, Wistar; Vasodilation - drug effects; Rat; Electrophysiology; Cardiovascular disease; Smooth muscle; iberiotoxin; mesenteric arteries; Vasodilation; LPS; rat vascular mesenteric bed; Vascular resistance; Blood vessel; Lipopolysaccharide; Membrane potential; calcium-dependent potassium channel; Rodentia; Tissue specificity; Normal; In vitro; Endothelium; Muscular relaxation; endothelin; Vertebrata; Mammalia; Animal; Arterial hypotension; Interindividual comparison; Models; aorta; endotoxin
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704850

The direct and endothelium‐dependent effects of lipopolysaccharide (LPS) were investigated on resistance and conductance arteries from normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats. In both NWR and SHR, LPS induced dose‐dependent relaxations of the mesenteric vascular bed, which were inhibited by L‐NNA in SHR but not in NWR. Iberiotoxin (IBTX) inhibited the responses to LPS in both groups, indicating the participation of high conductance Ca2+‐dependent K+ channels. In mesenteric artery rings, the resting membrane potentials and the hyperpolarizing responses of NWR to LPS did not differ in endothelized and denuded preparations but L‐NNA inhibited the responses only in endothelized rings. These responses were reduced by bosentan, suggesting that endothelin release may mask a possible hyperpolarizing response to LPS. The hyperpolarizing responses to LPS were blocked by IBTX in both endothelized and de‐endothelized NWR rings. In the SHR only intact rings showed hyperpolarization to LPS, which was inhibited by IBTX and byL‐NNA. In SHR aortic endothelized or denuded rings, LPS induced hyperpolarizing responses which, in endothelized rings, were partially blocked by L‐NNA, by IBTX or by glibenclamide, but totally abolished by IBTX plus glibenclamide. No response to LPS was observed in NWR aortic rings. Our results indicate that LPS activates large conductance Ca2+‐sensitive K+ channels located in the smooth muscle cell membrane both directly and indirectly, through NO release from the endothelium in NWR, whereas NO is the major mediator of the LPS responses in SHR resistance vessels. British Journal of Pharmacology (2002) 137, 213–220. doi:10.1038/sj.bjp.0704850