title: Renal and systemic effects of endothelin-1 in diabetic-hypertensive rats.
abstract: The Cohen-Rosenthal Diabetic Hypertensive rat (CRDH) is a unique animal model in which genetic hypertension and diabetes developed after crossbreeding of Cohen diabetic rats sensitive substrain (CDR) and spontaneously hypertensive rats (SHR). The present study examined: 1) The acute effects of ET-1 on the systemic and renal hemodynamics in CRDH rats, CDR, and SHR; 2) The expression of ET-1 and its receptors in the renal tissue of CRDH rats. Intravenous injection of ET-1 (1.0 nmol/kg) into anesthetized SHR rats resulted in a significant immediate depressor response (mean arterial pressure (MAP) decreased from 165 ± 3 to 124 ± 12 mmHg, p < 0.0001) followed by a minor hypertensive phase (MAP increased to 170 ± 2 mmHg). Simultaneously, the administration of ET-1 caused a significant decrease in renal blood flow (RBF) from 5.8 ± 0.9 ml/min to 3.2 ± 0.5 ml/min (p = 0.026). These responses were blunted in CRDH rats and CDR. Analysis of intra-renal blood flow by laser-Doppler in CRDH rats revealed that ET-1 injection caused a decrease in cortical blood flow (Δ = -12 ± 2.9%). However, in contrast to its well-known renal medullary vasodilatory effect, ET-1 produced a significant decline in the medulla blood flow (Δ = -17.5 ± 3.4%) (p = 0.0125). These findings suggest that CDR and CRDH rats have reduced sensitivity to vascular and renal action of ET-1. Furthermore, in the CRDH rats, the expected ET-1-induced medullary vasodilatation was abolished and even reversed into prolonged vasoconstriction.
authors.affiliation: Hypertension Research Unit, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Cipy
authors.initials: C
authors.lastname: Hofman
authors.forename: Talma
authors.initials: T
authors.lastname: Rosenthal
authors.forename: Joseph
authors.initials: J
authors.lastname: Winaver
authors.forename: Irit
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Rawi
authors.initials: R
authors.lastname: Ramadan
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
authors.forename: Rona
authors.initials: R
authors.lastname: Limor
authors.forename: Hoda
authors.initials: H
authors.lastname: Awad
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D015870:Gene Expression; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D017931:DNA Primers; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B