atrial-natriuretic-factor and azepexole

Heart failure is associated with increased sympathetic nerve activity. We hypothesized that chronic sympathetic stimulation in heart failure resulted in decreased vascular sympathetic responsiveness. A pithed rat model was employed to evaluate peripheral vascular alpha-adrenoceptor and neuropeptide Y (NPY) receptor responsiveness. Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. Sham operated rats (Sham) served as controls. Two months after this surgical procedure, both heart failure (n = 30) and Sham (n = 30) rats underwent standard pithing procedure. Pressor responses to preganglionic sympathetic nerve stimulation (PNS) and activation of postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors were studied. In response to PNS, cardiac index was similar between heart failure and sham rats (P = n.s.). Mean arterial pressure (MAP) increased in a frequency-dependent fashion after PNS in heart failure rats as well as in control rats. All the agonists used, i.e. the alpha1-adrenoceptor agonist phenylephrine, the alpha2-adrenoceptor agonists clonidine and BHT933 as well as NPY, induced dose-dependent increases in MAP in heart failure and in sham rats. However, in rats with heart failure, the response to all the agonists studied was significantly decreased and the dose response curves were shifted to the right (P < 0.01). We conclude that in vivo vascular response to postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors are decreased in rats with heart failure.

Topics: Adrenergic alpha-Agonists; Animals; Atrial Natriuretic Factor; Autonomic Fibers, Preganglionic; Azepines; Blood Pressure; Cardiac Output; Catecholamines; Clonidine; Decerebrate State; Electric Stimulation; Heart Failure; Male; Myocardial Infarction; Phenylephrine; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, alpha-2; Receptors, Neuropeptide Y

Ring segments of splanchnic, peripheral, coronary, pulmonary and uterine conduit arteries obtained during surgery were studied in tissue baths. Resistance arteries dissected from various sites were studied in a myograph. Both conduit and resistance vessels contracted in response to the alpha 1-agonist phenylephrine (10(-7) to 10(-4) mol/l), an effect that was antagonized by the alpha 1-antagonist doxazosin (10(-8) to 10(-6) mol/l). However, the alpha 2-agonists BHT 933 (10(-7) to 10(-4) mol/l) and UK 14304 (10(-7) to 10(-4) mol/l) only contracted the resistance vessels and not the conduit arteries. The response to BHT 933 was competitively antagonized by the alpha 2-antagonist yohimbine (3.10(-8) to 3.10(-7) mol/l) and the magnitude of the contractile response was inversely related to vessel size. Similarly, neuropeptide Y (10(-9) to 10(-6) mol/l) contracted only the resistance vessels, and induced marked tachyphylaxis. Atrial natriuretic peptide (ANP; 10(-8) to 10(-6) mol/l) produced concentration-dependent relaxation in all conduit arteries studied, being ineffective in resistance arteries from subcutaneous or omental sites, but relaxed those from renal tissue and skeletal muscle. Calcitonin gene-related peptide (10(-8) to 10(-6) mol/l) and vasoactive intestinal peptide (10(-9) to 10(-6) mol/l) relaxed both conduit and resistance arteries. This response was dependent on the integrity of the endothelium in the systemic conduit but not the resistance vessels. These results indicate that the receptors for adrenergic agonists and vasoactive peptides are varyingly distributed throughout the human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arteries; Atrial Natriuretic Factor; Azepines; Brimonidine Tartrate; Calcitonin Gene-Related Peptide; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Neuropeptide Y; Neuropeptides; Phenylephrine; Quinoxalines; Vascular Resistance; Vasoactive Intestinal Peptide