Inactivation of G(i) proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats.
Treatment with pertussis toxin (PTX) which eliminates the activity of G(i) proteins effectively reduces blood pressure (BP) and vascular resistance in spontaneously hypertensive rats (SHR). In this study we have compared the functional characteristics of isolated arteries from SHR with and without PTX-treatment (10 microg/kg i.v., 48 h before the experiment). Rings of thoracic aorta, superior mesenteric artery and main pulmonary artery were studied under isometric conditions to measure the reactivity of these vessels to receptor agonists and to transmural electrical stimuli. We have found that the treatment of SHR with PTX had no effect on endothelium-dependent relaxation of thoracic aorta induced by acetylcholine. In PTX-treated SHR, the maximum contraction of mesenteric artery to exogenous noradrenaline was reduced and the dose-response curve to cumulative concentration of noradrenaline was shifted to the right. Similarly, a reduction in the magnitude of neurogenic contractions elicited by electrical stimulation of perivascular nerves was observed in the mesenteric artery from PTX-treated SHR. PTX treatment of SHR also abolished the potentiating effect of angiotensin II on neurogenic contractions of the main pulmonary artery. These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension.
Zemančíková
A
A
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Török
J
J
Zicha
J
J
Kunes
J
J
D000109:Acetylcholine / Q000378:metabolism; D018663:Adrenergic Agents / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000109:Acetylcholine; D009638:Norepinephrine