Biochemistry of Cardiovascular Diseases - II

Biochemical Basis of Cardiovascular Diseases

• Nitric oxide (NO˙) is a highly reactive free radical formed from arginine by the enzyme nitric oxide synthase (NOS) which utilizes NADPH and molecular oxygen.

Nitric Oxide Synthase (NOS)

• There are three isoforms of NOS: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS).
• Constitutive forms of NOS (nNOS and eNOS) are involved in physiological processes, while inducible form (iNOS) is involved in immune responses.

Nitric Oxide (NO˙) Receptors

• NO˙ diffuses freely across cell membranes and acts in a paracrine or autocrine fashion, affecting only cells near its point of synthesis.
• NO˙ binds to protein receptors, triggering an allosteric change in the protein, which in turn triggers the formation of a "second messenger" (cGMP) within the cell.

Mechanism of Action of NO

• NO activates guanylate cyclase by diffusing into adjacent smooth muscle.
• Increased cyclic GMP (cGMP) activates protein kinase G (PKG) in smooth muscles, dephosphorylates myosin light chains, and leads to relaxation of smooth muscles, causing vasodilation.

Physiological Actions of NO

• Vasodilation: eNOS releases NO, maintaining blood pressure, and dilates cerebral, coronary, renal, and muscle arteries.
• Stimulates release of hormones: CRH, GHRH, and LHRH in the CNS.
• Role in macrophages: iNOS in macrophages produces NO and peroxynitrite, which are lethal to microorganisms, providing host immune defense.

Reperfusion Injury

• Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen.
• The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage.
• Xanthine oxidase activity increases during ischemia and on reperfusion, causing conversion of hypoxanthine to xanthine and superoxide anion.
• Allopurinol, a xanthine oxidase inhibitor, reduces the severity of reperfusion injury.

Understand the biochemical basis of cardiovascular diseases, including the role of nitric oxide, ischemia and reperfusion injury, and the L-arginine: NO pathway. Learn about the isoforms of nitric oxide synthase and their significance.