cyclic-gmp and Aortic-Coarctation

We investigated the role of nitric oxide on rapid (25- and 40-minute) baroreceptor resetting during the onset of acute hypertension in rats treated with NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of guanylate cyclase. The effect of treatment with glibenclamide, an ATP-dependent K+ channel blocker, was also investigated. Arterial hypertension was provoked in a ramp progression by the drug NG-nitro-L-arginine alone or in association with aortic coarctation. Whole aortic nerve activity and carotid pressure were recorded in the anesthetized rats. The extent of rapid resetting was evaluated by means of the ratio (delta Systolic Threshold Pressure/delta Control Diastolic Pressure) x 100 as well as by the extent of displacement of the pressure-nerve activity curve defined by the ratio (delta Mean Arterial Pressure at 50% of maximum activity/delta Mean Arterial Pressure) x 100. All groups gave the same increase in mean arterial pressure at 25 and 40 minutes after the onset of hypertension. A greater extent of resetting to hypertensive levels was observed in the treated groups compared with coarctation alone. At 40 minutes after the onset of hypertension, the coarctation and nitro-L-arginine groups exhibited a further increase in the extent of resetting. The rats submitted to glibenclamide plus coarctation presented a slight but significant decrease in gain. These findings suggest that an active L-arginine-nitric oxide-cyclic GMP pathway blunts rapid resetting during the onset of hypertension. In addition, they also indicate that ATP-dependent K+ channels can also modulate rapid resetting of the baroreceptors to hypertensive levels.

Topics: Analysis of Variance; Animals; Aorta; Aortic Coarctation; Arginine; Blood Pressure; Cyclic GMP; Glyburide; Guanylate Cyclase; Male; Methylene Blue; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Pressoreceptors; Rats; Rats, Wistar

Isolated aortas from hypertensive rats have a decreased relaxation response to acetylcholine chloride (ACh), the calcium ionophore A23187, and sodium nitroprusside (SNP). Since the vascular relaxation responses to these vasodilators may be a result of increases in guanosine 3',5'-cyclic monophosphate (cGMP), we measured the cGMP response to these agents in isolated aortas from normotensive rats and rats with either mineralocorticoid-induced hypertension (DOCA), renovascular hypertension (1K1C), or coarctation-induced hypertension (Coarc). The aortas from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to ACh and A23187. Rises in cGMP in response to SNP were also attenuated in aortas from the hypertensive rats, even at concentrations that induced maximum relaxation of blood vessels from normotensive and hypertensive rats. The relaxation responses to atrial natriuretic factor (ANF) and the cGMP generated in isolated aortas by ANF were attenuated in hypertension. Removal of the endothelium markedly attenuated cGMP generation in response to ANF in vessels from normotensive and Coarc rats, but the relaxation responses to ANF were unaltered in vessels after the removal of the endothelium. The reversal of experimentally induced hypertension was associated with increases in cGMP levels following exposure of the isolated vessels to ACh. Also, vessels treated with methylene blue relaxed in response to SNP despite inhibition of cGMP accumulation. The decreased relaxation response to endothelium-dependent vasodilators is accompanied by decreases in cGMP accumulation; the decreased vascular cGMP content in response to endothelium-dependent vasodilators is not due to increases in phosphodiesterase activity of vascular smooth muscle; and SNP may relax blood vessels through "cGMP-dependent" and "cGMP-independent" mechanisms.

Topics: Animals; Aortic Coarctation; Atrial Natriuretic Factor; Biological Products; Calcimycin; Cyclic GMP; Desoxycorticosterone; Hypertension; Male; Nitric Oxide; Nitroprusside; Rats; Rats, Inbred Strains; Vasodilation