Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

Abstract

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

Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia

“…39,40 Interestingly, both in vitro and experimental data suggest that adrenergic agonists induce activation of CA I and II in erythrocytes and vascular smooth muscle. 41 The elevated CA activity demonstrated in our study may therefore provide an additive mechanism, on top of sympathetic activation, to modulate hemodynamic control in OSA. Such a potential interaction needs to be addressed in future detailed studies of vascular dynamics in patients with OSA.…”

Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant

“…1,2 The cardiotoxic effects of ephedrine are well described in human beings and animal models. [3][4][5] In rats, infusions of similar catecholamine-like substances have been found to produce myocardial injury characterized by necrosis. Similar lesions occur in human beings.…”

“…Other hemodynamic changes and electrocardiographic abnormalities can be seen in these cases. [3][4][5] Injection of catecholamine products has been shown to cause intracranial arterial spasm in monkeys. 4 To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion.…”

“…I n clinical and animal studies, investigators have documented the ability of ephedrine-like substances to induce vasospasm. [1][2][3][4][5] By stimulating the release of norepinephrine, ephedrine induces vascular resistance and can cause increases in blood pressure, heart rate, and cardiac output. 1,2 Despite wide use, especially for symptomatic relief from seasonal allergies, decongestants with strong sympathomimetic properties place patients at risk.…”