[Nitric oxide. The role of guanylate cyclase in its physiological effects].
In this review the molecular mechanism underlying the antihypertensive and anti-aggregatory actions of nitric oxide (NO) are discussed. It has been shown that these effects are directly connected with the activation of soluble guanylate cyclase and the accumulation of cyclic 3',5'-guanosine monophosphate (cGMP). The data concerning the basic chemical characteristics of guanylate cyclase, such as the subunits structure, isoforms, modern concepts on the catalytic and regulatory centers of the enzyme are presented. The role of heme and sulfhydryl groups in the functioning of guanylate cyclase and the significance of the nitrosyl-heme complex formed as a result of interaction of guanylate cyclase heme with NO are analyzed. Using new approaches for studying the antihypertensive and antiaggregatory actions of nitric oxide in combination with the newly obtained data on the regulatory role of guanylate cyclase in the platelet aggregation process, the most important results were obtained. The priority data on the new inhibitors of nitric oxide-dependent guanylate cyclase activation (among which turn to be the drugs) and the possible molecular mechanism of their pharmacological action are presented.
Severina
I S
IS
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119992 Russia.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D006162:Guanylate Cyclase
Oksid azota. Rol' rastvorimoĭ guanilattsiklazy v mekhanizmakh ego fiziologicheskikh éffektov.