Carbonic Anhydrase I Inhibition By Nitric Oxide: Implications For Mediation Of The Hypercapnia‐Induced Vasodilator Response

Abstract

1. At present, CO2 is considered to be the most important factor in regulating cerebral blood flow by modification of the interstitial fluid and extracellular pH, but the mechanism by which hypercapnia produces vasodilation is still controversial. In the present paper we investigated the effect of hypercapnia on carbonic anhydrase (CA) activity. We also studied the combined effects of CO2 with either indomethacin or an L-arginine analogue on CA activity. 2. Nine groups of 12 rabbits each were established. Groups 1-4 were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 20, 60, 120 and 180 min. Group 5 rabbits received 15 mg/kg bodyweight, i.v., indomethacin and, after 1 h, were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h. Group 6 animals were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h and then received indomethacin. Group 7 rabbits received 100 mg/kg bodyweight, i.v., NG-monomethyl-L-arginine (L-NMMA) and, after 1 h, were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h. Group 8 rabbits were ventilated for 2 h with a mixture of 10% CO2, 21% O2 and 69% N2 and were then administered L-NMMA. Group 9 rabbits received L-NMMA treatment concomitant with ventilation for 2 h with a mixture of 10% CO2, 21% O2 and 69% N2. In all groups, the erythrocyte CA activity was measured, as well as PaCO2 before and after ventilation or treatment. 3. The present study shows that CO2 reduces CA I activity down to complete inhibition and antagonizes the activating effects of indomethacin and L-NMMA on this isozyme. Our data prove that nitric oxide- and prostaglandin-induced CA I inhibition is involved in the vasodilation produced by hypercapnia. These results suggest that, due to subsequent pH changes, CA I is directly implicated in the modulation of vascular processes in the organism.

Role of Nitric Oxide in the Regulation of Cerebral Blood Flow in Humans

“…For instance, the fast changes in pH that occur during hypocapnia and hypercapnia are important modulators of NO synthase. 32 Also, pharmacological manipulations of opiate receptors, 33 prostaglandins production, 34 and ATP-dependent K ϩ channel activation 35 were found to be involved in the modulation of CO 2 -NO cerebral vasomotor reactivity. The detailed discussion of this issue is beyond the scope of this article, and the final mechanism of this pathway remains to be explored.…”

Evaluation of Strychnos pseudoquina ST. HIL. Leaves Extract on Gastrointestinal Activity in Mice

“…This index was expressed as the sum of all lesions, as described in the literature. 20) b) Non-steroidal Antiinflammatory Drug (NSAID)-Induced Gastric Ulcers in Mice: In this model, 21) gastric ulcer was induced using piroxicam (30 mg/kg, s.c.) administered to mice. The crude MeOH extract or EAF from S. pseudoquina (250, 1000 mg/kg), cimetidine (100 mg/kg) or saline was administered orally 30 min before induction of the gastric ulcer.…”

The Mechanisms by Which Latanoprost Free Acid Inhibits Human Carbonic Anhydrase I and II

“…[24][25][26] It is known that efficient activators of CA possess a bulky aromatic/heterocyclic moiety and a primary/secondary amino group in their molecular structure. 26) Pauscas and Coltau 9) pointed out that the prostaglandin F2alpha activates the hydration activity of CA in vivo and in vitro, but the mo- ), in which the bromide ion binds to the zinc ion. lecular structure is very different from those of the common efficient activators of CA.…”

“…8) Puscas and Coltau have shown that prostaglandin F2alpha, enhances CA activity, resulting in an elevation of blood pressure. 9) Therefore, latanoprost is supposed to have some influence on CA activity in the eyes. CA is an enzyme found in many tissues of the body.…”