cardiovascular system
• mutants exhibit reduced relaxation in aortic rings in response to acetylcholine, an inducer of NO synthesis, indicating absence of nitric oxide (NO)/cGMP dependent relaxation of cardiac muscle
|
• hypertensive effects of L-NNA (NG-nitro-L-arginine) and the hypotensive effects of DEA-NO are absent in mutants
|
hypertension
(
J:48058
)
• mean arterial blood pressure is significantly higher in unrestrained, conscious mice than in wild-type mice but normal in anaesthetized mice
• older mice exhibit normal arterial blood pressure
|
• although basal intracellular calcium concentration in vascular smooth muscle cells is normal, a cGMP analog, 8-Br-cGMP, which attenuates the transient intracellular calcium concentration in wild-type cells to 35% has no effect on the intracellular calcium concentrations in mutant cells
|
muscle
• mutants exhibit reduced relaxation in aortic rings in response to acetylcholine, an inducer of NO synthesis, indicating absence of nitric oxide (NO)/cGMP dependent relaxation of cardiac muscle
|
• although basal intracellular calcium concentration in vascular smooth muscle cells is normal, a cGMP analog, 8-Br-cGMP, which attenuates the transient intracellular calcium concentration in wild-type cells to 35% has no effect on the intracellular calcium concentrations in mutant cells
|
• intestinal motility is impaired; passage of dye into the duodenum is delayed, spastic contractions of long intestinal segments followed by scarce and slow relaxations are seen instead of regular peristalsis
|
• no phasic contraction response or relaxation is seen after exposure to cGMP in smooth muscle from the colon and little or no relaxation is seen in cGMP exposed phenylephrine-precontracted aortic segments
• cGMP has no effect on Ca2+ transients in mutant smooth muscle unlike in wild-type smooth muscle
|
• mutant gastric fundus muscle strips exhibit impaired relaxation in response to electrical field stimulation; the first relaxation phase (rapid and transient) is absent, while the second phase (slower onset that lasts longer) is similar to wild-type
(J:48058)
• 8-Br-cGMP treatment of gastric fundus muscle does not completely relax the muscles as in wild-type
(J:48058)
• corpora cavernosa fails to relax on activation of the nitric oxide/cGMP signaling cascade but shows normal relaxation in response to forskolin induced cAMP elevation
(J:60928)
|
reproductive system
|
• corpora cavernosa fails to relax on activation of the nitric oxide/cGMP signaling cascade but shows normal relaxation in response to forskolin induced cAMP elevation
|
|
• however, females are fertile and sperm is morphologically normal, exhibits normal motility, can undergo acrosomal reactions and able to fertilize eggs in vitro
|
digestive/alimentary system
• intestinal distension, especially of the caecum
|
• hypertrophy of the gastric fundus
|
• intestinal motility is impaired; passage of dye into the duodenum is delayed, spastic contractions of long intestinal segments followed by scarce and slow relaxations are seen instead of regular peristalsis
|
• passage of dye into the duodenum is delayed
• at a time when the stomach is empty in wild-type mice, in mutants the stomach still contains contrast dye and the small intestine just begins to fill
|