cGMP modulates basal and activated microvessel permeability independently of [Ca2+](i)

P. He, M. Zeng, F. E. Curry

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To investigate the mechanisms whereby guanosine 3',5'-cyclic monophosphate (cGMP) modulates microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (L(p)) and endothelial cytoplasmic Ca2+ concentration ([Ca2+](i)) in response to the cGMP analogs 8-bromo-cGMP (8-BrcGMP) and 8-(p-chlorophenylthio)cGMP (8-pCPT-cGMP) in the presence and absence of inflammatory stimuli in intact individually perfused microvessels in frog and rat mesenteries. The cGMP analog caused a transient increase in L(p) and potentiated ATP or bradykinin-induced increases in L(p) in frog and rat mesenteric microvessels, respectively. The mean peak value of the test L(p)/control L(p) after exposure to 8-BrcGMP was 5.3 ± 0.5 in frog microvessels and 2.8 ± 0.4 in rat microvessels. The ATP- induced increase in L(p) in frog microvessels was further raised by 8-BrcGMP from 7.0 ± 0.9 to 12.4 ± 1.9 times the control. In rat mesenteric microvessels, the bradykinin-induced increase in L(p) was potentiated by 8- BrcGMP from 4.8 ± 0.4 to 8.3 ± 1.3 times the control and was suppressed by the guanylate cyclase inhibitor LY-83583 to 2.6 ± 0.5 times the control. A similar but larger effect was found when using 8-pCPT-cGMP. In contrast to the actions of increased cGMP on microvessel permeability, cGMP analogs had no effect on basal endothelial [Ca2+](i) and did not alter the magnitude and time course of ATP or bradykinin-induced increases in endothelial [Ca2+](i). These results suggested that an elevation of cGMP levels in endothelial cells is a necessary step to increase microvessel permeability in intact microvessels, and this regulatory process occurs downstream from Ca2+ influx, which differs from that reported in large-vessel endothelium in culture and in vascular smooth muscle cells. Experiments carried on microvessels in both frog and rat mesenteries provided a direct comparison of the endothelial cell regulatory mechanisms between species.

Original languageEnglish (US)
Pages (from-to)H1865-H1874
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 43-6
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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