Isosorbide Nitrates, Nitroglycerin, and Sodium Nitroprusside Induce Vasodilation Concomitantly With Inhibition of Carbonic Anhydrase I in Erythrocytes

Puşcaş, I; Vlaicu, R; Lazăr, Aurel

doi:10.1016/s0895-7061(96)00350-0

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…Thus, vasoconstrictor compounds act as CA I activators, whereas vasodilating compounds act as CA I inhibitors. Acetazolamide, a CA inhibitor, is also a potent vasodilator 16 and prostaglandins (PG)E 1 , PGE 2 and PGI 2 , NO and organic nitrates are CA inhibitors 17–19 . Indomethacin (a cyclo‐oxygenase inhibitor) activates CA I and acts as an antagonist towards acetazolamide, prostaglandins and NO at the level of this enzyme 20…”

Section: Introductionmentioning

confidence: 99%

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

Puşcaş¹,

Coltâu²,

Domuţa³

et al. 2000

Clin Exp Pharma Physio

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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.

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Section: Introductionmentioning

confidence: 99%

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

Puşcaş¹,

Coltâu²,

Domuţa³

et al. 2000

Clin Exp Pharma Physio

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“…Puscas et al cesses in the organism. In our conception, the pH increase induced by CA I inhibition might influence the binding of hypotensive stimuli to their specific receptors, followed by signal transduction to the cytoplasm of smooth muscle cells with subsequent vasodilating effects (9,14). Similarly, the reduction in pH induced by vascular smooth muscle CA I activation with hypertensive agents may influence the membrane specific receptor and signal transduction in the vascular smooth muscle cytosol, with subsequent vasoconstrictive effects (14).…”

Section: Discussionmentioning

confidence: 99%

Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

Puşcaş¹,

Coltâu²,

Gilau³

et al. 2001

Braz J Med Biol Res

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We studied the relationship between alpha-and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors), so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction. Correspondence

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“…Our studies have also shown that vasoconstriction is accompanied by carbonic anhydrase I activation, and vasodilation is accompanied by carbonic anhydrase I inhibition. The most used vasoconstrictive therapeutic agents increase carbonic anhydrase I activity, whereas vasodilating drugs reduce the activity of this isozyme 9 , 10 , 11 , 12 , 13…”

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confidence: 99%

Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition

Puşcaş¹

2000

Clinical Pharmacology & Therapeutics

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In this article we studied in vitro and in vivo the effect of calcium channel blockers (verapamil and amlodipine) on erythrocyte carbonic anhydrase I activity, on carbonic anhydrase I isolated from vascular smooth muscles, and on arterial blood pressure values in human beings and in animals. Our in vitro and in vivo results have shown that verapamil and amlodipine are strong inhibitors of carbonic anhydrase I both in erythrocytes (in human beings) and in vascular smooth muscles (in animals). In human beings calcium channel blockers reduce arterial blood pressure in subjects with hypertension and progressively reduce erythrocyte carbonic anhydrase I activity. We assume that verapamil and amlodipine possess a dual mechanism of action: the first mechanism consists of their action on calcium channels, and the second mechanism, proposed by us, shows that verapamil and amlodipine inhibit vascular smooth muscle carbonic anhydrase I activity with consecutive pH increase. The increase of pH might be an additional factor involved in intracellular calcium influx through calcium channels. This dual mechanism of action would bring new data regarding the hypotensive effect of verapamil and amlodipine, effects that might also be parallel and dependent on carbonic anhydrase I inhibition.

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Isosorbide Nitrates, Nitroglycerin, and Sodium Nitroprusside Induce Vasodilation Concomitantly With Inhibition of Carbonic Anhydrase I in Erythrocytes

Cited by 8 publications

References 11 publications

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

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

Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition

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