Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension

Thomas C. Resta, Rayna J Gonzales, William G. Dail, Thomas C. Sanders, Benjimen R. Walker

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest that CH is associated with increased endothelial nitric oxide synthase (eNOS) activity within the pulmonary arterial vasculature. In addition, the correlation of increased pulmonary arterial pressure with selectively enhanced arterial responsiveness to EDNO-mediated agonists suggests that arterial hypertension, rather than hypoxia per se, is a contributing factor in this response. Therefore, we hypothesized that 1) CH selectively upregulates eNOS within the pulmonary arterial vasculature and 2) monocrotaline (MC)-induced pulmonary arterial hypertension selectively enhances pulmonary arterial dilation to EDNO-dependent dilators and upregulates arterial eNOS. We examined the responses to the EDNO-dependent dilators arginine vasopressin and ionomycin in U-46619-constricted isolated perfused lungs from control and MC-treated rats. Microvascular pressure was assessed by the double-occlusion technique, allowing calculation of segmental resistances. Lungs from MC-treated rats exhibited augmented arterial dilation to arginine vasopressin compared with control lungs. However, the responses to ionomycin were not different between the two groups. Quantitative immunocytochemistry was used to compare pulmonary eNOS immunoreactivity in vessels from control, CH, and MC-treated rats. eNOS staining was more intense in the arteries of CH and MC-treated rats compared with those of control animals, whereas CH and MC treatment had no effect on eNOS staining in veins. We conclude that pulmonary arterial hypertension, or altered vascular mechanical forces associated with hypertension, may be responsible for the augmented EDNO-dependent arterial dilation and upregulation of arterial eNOS in lungs from CH and MC-treated rats.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume41
Issue number2
StatePublished - Feb 1997
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Monocrotaline
Pulmonary Hypertension
Up-Regulation
Lung
Nitric Oxide
Dilatation
Ionomycin
Arginine Vasopressin
Staining and Labeling
Hypertension
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Hypoxia
Blood Vessels
Veins
Arterial Pressure
Arteries
Immunohistochemistry
Pressure

Keywords

  • Chronic hypoxia
  • Endothelium-dependent vasodilation
  • Isolated rat lungs
  • Monocrotaline
  • Quantitative immunocytochemistry
  • Segmental vascular resistance

ASJC Scopus subject areas

  • Physiology

Cite this

Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension. / Resta, Thomas C.; Gonzales, Rayna J; Dail, William G.; Sanders, Thomas C.; Walker, Benjimen R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 41, No. 2, 02.1997.

Research output: Contribution to journalArticle

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