Substance P in subtotal nephrectomy-salt hypertension.
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.
Katki
Khurshed A
KA
Michigan State University, College of Human Medicine, Department of Medicine, East Lansing, MI 48824, USA.
Supowit
Scott C
SC
DiPette
Donald J
DJ
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
D012333:RNA, Messenger; D012492:Salts; C065446:spantide II; D013373:Substance P