International Journal of Anatomy and Physiology

mInternational Journal of Anatomy and Physiology | Vol. 15, No. 9, September 2026 | pp. 245–256

DOI: 10.46882/2026/IJAP/000188

Article Type: Review Article

Title: Functional Anatomy and Molecular Pathways Governing Hypoxic Pulmonary Vasoconstriction: A Review of Cellular Feedback Loops

Names of Authors: Dmitry V. Ivanov¹, Svetlana A. Petrova²

Authors’ Affiliations: ¹Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; ²Research Institute of Human Physiology, Saint Petersburg State University, Saint Petersburg, Russia

Abstract:
Hypoxic pulmonary vasoconstriction (HPV) is a highly specialized local autoregulatory mechanism that shunts blood flow from poorly ventilated segments of the lung toward well-oxygenated zones, thereby optimizing ventilation-perfusion matching. This review examines the complex functional anatomy of pulmonary smooth muscle cells (PASMCs) and the intracellular signaling pathways that trigger HPV. The unique structural composition of pre-capillary pulmonary arteries, which display high expression levels of oxygen-sensing proteins, is central to this mechanism. The primary sensor involves mitochondrial complex III, which alters reactive oxygen species (ROS) output in response to drops in alveolar oxygen tension (PAO2 < 60 mmHg). Alterations in ROS generation suppress voltage-gated potassium channels (KV1.5 and KV2.1) in the PASMC sarcolemma. This suppression induces membrane depolarization, which subsequently opens L-type voltage-gated calcium channels (VGCCs), driving a rapid influx of extracellular Ca2+. Concurrently, calcium sensitization via the RhoA/Rho-kinase (ROCK) signaling loop maintains prolonged contraction without requiring high intracellular calcium levels. Disruptions within these pathways contribute to the development of chronic hypoxic pulmonary hypertension. Analyzing these molecular dynamics illuminates targeted pharmacological windows, guiding the production of selective pulmonary vasodilators for neonatal and adult respiratory distress syndromes.

Keywords: Hypoxic Pulmonary Vasoconstriction, Pulmonary Smooth Muscle, Calcium Channels, Potassium Channels, Rho-Kinase, Mitochondria

Manuscript Timeline: Received: July 18, 2026; Revised: August 25, 2026; Accepted: September 08, 2026; Published: September 23, 2026

Citation: Ivanov D.V., & Petrova S.A. (2026). Functional Anatomy and Molecular Pathways Governing Hypoxic Pulmonary Vasoconstriction: A Review of Cellular Feedback Loops. International Journal of Anatomy and Physiology, 15(9), 245–256. DOI: 10.46882/2026/IJAP/000188

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