title: Substance P in subtotal nephrectomy-salt hypertension.
abstract: We have previously demonstrated that calcitonin gene-related peptide (CGRP) plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt) hypertension through an increase in vascular responsiveness to the dilator activity of this neuropeptide. Substance P (SP) is often co-localized with CGRP in perivascular sensory nerves. To determine the role and mechanism of action of SP in SN-salt hypertension, we induced hypertension in 4- to 6-week-old male Sprague-Dawley rats (n=8) by subtotal nephrectomy and 1% saline drinking water. Sham-operated rats were given either tap water (n=9) or 1% saline to drink (n=9). Eleven to 13 days after each protocol, all rats had intravenous (for drug administration) and arterial (for continuous monitoring of mean arterial pressure [MAP]) catheters surgically implanted and were studied in the conscious and unrestrained state. Baseline MAP was significantly elevated in the SN-salt rats (157 +/- 6 mm Hg) compared with tap water--fed controls (128 +/- 3 mm Hg) and 1% saline--fed controls (132 +/- 5 mm Hg). Vehicle administration did not alter the MAP in any group. In contrast, administration of spantide-II (0.2 micromol/L in saline), an SP receptor antagonist, significantly elevated the MAP in SN-salt rats (13.9 +/- 0.8 mm Hg) compared with the tap water (1.7 +/- 1.7 mm Hg) and 1% saline controls (2.0 +/- 1.9 mm Hg). SP mRNA and peptide levels in dorsal root ganglia were not significantly different between the 3 groups. Administration of exogenous SP (12 and 24 nmol center dot L(-1) center dot kg(-1) intravenously) resulted in a significantly greater decrease in MAP in the SN-salt rats compared with both control groups. Taken together, these data suggest that in SN-salt hypertension, SP plays a counterregulatory role in the absence of an increase in its neuronal expression, thereby suggesting that one possible mechanism of this compensatory vasodilator response is enhanced vascular reactivity to SP.
authors.affiliation: Michigan State University, College of Human Medicine, Department of Medicine, East Lansing, MI 48824, USA.
authors.forename: Khurshed A
authors.initials: KA
authors.lastname: Katki
authors.forename: Scott C
authors.initials: SC
authors.lastname: Supowit
authors.forename: Donald J
authors.initials: DJ
authors.lastname: DiPette
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts; D013373:Substance P / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D012492:Salts; C065446:spantide II; D013373:Substance P