Impaired modulation of sympathetic excitability by nitric oxide after long-term administration of organic nitrates in pigs

Circulation
J ZanzingerH Seller

Abstract

Endogenous nitric oxide (NO) reduces sympathetic vasoconstriction by attenuating neuronal excitability in the brain stem and inhibition of postganglionic neurotransmission. We studied whether this modulation of sympathetic circulatory control by NO may be altered during chronic administration of NO donor drugs in pigs. Nitrate tolerance was induced by oral administration of isosorbide dinitrate (ISDN, 4 mg/kg per day for 4 weeks) in eight pigs. Four of them were chronically instrumented for the measurement of mean arterial blood pressure and cardiac output in the conscious state. ISDN treatment caused hemodynamic tolerance to NO donors and significantly increased the hypotensive responses to pharmacologic ganglionic blockade in conscious pigs. In general anesthesia, ISDN-treated animals and age-matched controls (n=5) had similar baseline renal sympathetic nerve activity and in both groups neither inhibition of NO synthases (NOS) nor administration of NO donors to the brain stem by intracerebroventricular (i.c.v.) infusions caused significant changes in baseline renal sympathetic nerve activity. However, whereas sympathoexcitatory responses to glutamate (0.5 mL, 0.1 mol/L, i.c.v.) or electrical stimulation of somatic nerve affer...Continue Reading

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Citations

Mar 17, 2005·Cardiovascular Drugs and Therapy·John A ChiladakisDimitrios Alexopoulos
Dec 12, 2002·Journal of the American College of Cardiology·Tommaso GoriJohn D Parker
Jul 30, 2002·Autonomic Neuroscience : Basic & Clinical·Johannes Zanzinger
Jan 5, 2000·European Journal of Clinical Investigation·P KovacsA Tosaki
Oct 8, 2009·Cellular and Molecular Life Sciences : CMLS·José A L CalbetCarsten Lundby
Mar 19, 2005·Journal of Hypertension·Megumi Tandai-HirumaYasuhiro Nishida
Oct 31, 2002·Circulation·Tommaso Gori, John D Parker
Sep 25, 2001·Experimental Biology and Medicine·K P PatelY Hirooka
Aug 12, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Takuto HamaokaJian Cui

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