Kishimoto I, Dubois S K, Garbers D L
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235-9050, USA.
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6215-9. doi: 10.1073/pnas.93.12.6215.
Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical for the maintenance of normal blood pressure during high salt intake. In this report, we show that infusion of ANP results in substantial natriuresis and diuresis in wild-type mice but fails to cause significant changes in sodium excretion or urine output in GC-A-deficient mice. ANP, therefore, appears to signal through GC-A in the kidney. Other natriuretic/diuretic factors could be released from the heart. Therefore, acute volume expansion was used as a means to cause release of granules from the atrium of the heart. That granule release occurred was confirmed by measurements of plasma ANP concentrations, which were markedly elevated in both wild-type and GC-A-null mice. After volume expansion, urine output as well as urinary sodium and cyclic GMP excretion increased rapidly and markedly in wild-type mice, but the rapid increases were abolished in GC-A-deficient animals. These results strongly suggest that natriuretic/diuretic factors released from the heart function exclusively through GC-A.
鸟苷酸环化酶 -A（GC-A）功能失调会导致小鼠血压升高，且高盐或低盐饮食均无法改变这一状况。然而，心房利钠肽（ANP）被认为是GC-A的一种配体，有人提出它对于高盐摄入期间维持正常血压至关重要。在本报告中，我们发现，向野生型小鼠输注ANP会导致大量利钠和利尿，但在GC-A缺陷型小鼠中，输注ANP不会引起钠排泄或尿量的显著变化。因此，ANP似乎是通过肾脏中的GC-A来发挥信号传导作用的。其他利钠/利尿因子可能从心脏释放。因此，急性血容量扩张被用作促使心脏心房释放颗粒的一种手段。通过测量血浆ANP浓度证实了颗粒的释放，野生型小鼠和GC-A基因敲除小鼠的血浆ANP浓度均显著升高。血容量扩张后，野生型小鼠的尿量以及尿钠和环磷酸鸟苷排泄迅速且显著增加，但在GC-A缺陷型动物中，这种快速增加消失了。这些结果有力地表明，从心脏释放的利钠/利尿因子仅通过GC-A发挥作用。
