DEFECTIVE SMOOTH-MUSCLE REGULATION IN CGMP KINASE I-DEFICIENT MICE

Regulation of smooth muscle contractility is essential for many import ant biological processes such as tissue perfusion, cardiovascular haem ostasis and gastrointestinal motility, While an increase in calcium in itiates smooth muscle contraction, relaxation can be induced by cGMP o r cAMP, cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides, To study the biological role of cGKT. and its postulated cross-activation by cA MP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abol ishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, re sulting in severe vascular and intestinal dysfunctions, However, cGKI- deficient smooth muscle responded normally to cAMP, indicating that cA MP and cGMP signal via independent pathways, with cGKI being the speci fic mediator of the NO/cGMP effects in murine smooth muscle.