Evidence that reduced renal medullary nitric oxide synthase activity of dahl s rats enables small elevations of arginine vasopressin to produce sustained hypertension.
On the basis of observations supporting the functional importance of nitric oxide (NO) in the regulation of renal medullary function, and a reduced nitric oxide synthase (NOS) enzyme activity in the outer medulla of the Dahl salt-sensitive (SS/Mcw) rats, we hypothesized that these inbred rats would have reduced capacity to synthesize renal medullary NO. This reduced capacity would sensitize them to the hypertensive effects of small elevations of circulating arginine vasopressin (AVP). SS/Mcw and Brown Norway (BN/Mcw) rats with implanted arterial and venous catheters were fed a 0.4% salt diet and infused intravenously for 14 days with a subpressor dose of AVP (2 ng/kg per min). Mean arterial pressure (MAP) was measured 2 hours daily in unanesthetized rats maintained in their home cages. MAP in SS/Mcw rats increased during day 1 of AVP infusion from a control level of 127+/-0.9 mm Hg to an average of 147+/-1.6 mm Hg after 14 days. MAP did not return to control values during the 3 days after the end of AVP infusion. BN/Mcw rats showed no changes of MAP during 14 days of AVP infusion (90.4+/-0.6 mm Hg and 92.3+/-0.4 mm Hg). Northern blot analysis of renal tissue from vehicle (saline) -infused rats demonstrated that NOS I and NOS III mRNA expression was significantly less in SS/Mcw rats in the renal outer medulla compared with BN/Mcw rats. We conclude that small, normally subpressor elevations of plasma AVP can produce chronic hypertension in SS/Mcw rats and that this phenomenon is related to the reduced medullary NOS enzyme activity, which in turn reduces the AVP-stimulated NO synthesis.
Yuan
B
B
Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.
Cowley
A W
AW
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D007262:Infusions, Intravenous; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000494:pharmacology; D013997:Time Factors
D012333:RNA, Messenger; D012982:Sodium, Dietary; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat