title: Pertussis toxin normalizes enhanced renovascular responses to angiotensin II in spontaneously hypertensive rats.
abstract: Previous studies indicate that spontaneously hypertensive rats (SHR) have an exaggerated renal vascular response to angiotensin II (Ang II). Inasmuch as angiotensin receptors are coupled to diverse signalling mechanisms via G-proteins, the purpose of this study was to determine whether the enhanced renal vascular response to Ang II in SHR is due to signalling pathways that involve Gi and/or Go. Age-matched SHR and normotensive Wistar-Kyoto rats were administered an intravenous injection of either pertussis toxin (10 micrograms/kg) or vehicle, and 6 days later were prepared for study. Renal vascular responses to Ang II were determined by infusing Ang II into the aorta just above the left renal artery while monitoring renal blood flow and arterial blood pressure. Inhibition of the bradycardic response to N6-cyclopentyladenosine (an adenosine A1 receptor agonist) verified that pertussis toxin interrupted Gi coupled pathways. Renovascular responses to Ang II were significantly greater (p = 0.0009) in vehicle-treated hypertensive rats when compared with vehicle-treated normotensive rats. Pertussis toxin significantly decreased renovascular responses to Ang II in both hypertensive (p < 0.0001) and normotensive (p = 0.0101) rats, but more so in hypertensive rats. In pertussis toxin-treated rats renovascular responses to Ang II were similar in hypertensive versus normotensive rats.
  
  
  CONCLUSIONS
  1) Gi and/or Go contributes importantly to the signalling mechanism through which Ang II affects renal vascular resistance; and, 2) An alteration in the Gi and/or Go-mediated signalling pathway in the renal vasculature appears to mediate the enhanced renal vascular response to Ang II in SHR.
authors.affiliation: Center for Clinical Pharmacology, University of Pittsburgh Medical Center, PA 15213-2582.
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins