Renovascular parathyroid hormone-related protein in spontaneously hypertensive rats: dilator or trophic factor?
Parathyroid hormone-related protein (PTHrP) is expressed throughout the renovascular system, and it dilates renal vessels, increases renal blood flow and glomerular filtration rate, and stimulates renin release. Mechanical forces and experimental hypertension have been shown to stimulate PTHrP expression in smooth muscles, suggesting a negative feedback control of vascular tone by PTHrP in hypertension. In this study, we compared the impact of a PTHrP receptor antagonist, PTHrP (7-34), and a PTHrP receptor agonist, PTHrP (1-36), on the vascular resistance of perfused kidneys isolated from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Endogenous PTHrP appears not to act as a renal vasodilator in either WKY or SHR. However, the vasodilation following infused PTHrP (1-36) is blunted markedly in SHR, possibly due to desensitization or down-regulation of PTH/PTHrP receptors. Negative feedback control of vascular tone by PTHrP in SHR thus appears unlikely. The results raise the question of whether endogenous renovascular PTHrP behaves rather as a growth factor than as a vasodilator.
Fiaschi-Taesch
N
N
Pharmacology Department, University Louis Pasteur School of Medicine, Strasbourg, France.
Endlich
N
N
Massfelder
T
T
Endlich
K
K
Stewart
A F
AF
Helwig
J J
JJ
D000818:Animals; D005246:Feedback / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006977:Hypertension, Renal / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry / Q000503:physiopathology; D008297:Male; D009924:Organ Culture Techniques; D044162:Parathyroid Hormone-Related Protein; D010656:Phenylephrine / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018016:Receptors, Parathyroid Hormone / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D006133:Growth Substances; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D018016:Receptors, Parathyroid Hormone; D014662:Vasoconstrictor Agents; D010656:Phenylephrine