Functional subtypes of renal alpha1-adrenoceptor in spontaneously hypertensive rats with streptozotocin-induced experimental diabetic nephropathy.
OBJECTIVE
This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition.


METHODS
In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na(+) (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (alpha-adrenoceptor agonist), phenylephrine (alpha(1)-adrenoceptor agonist) and methoxamine (alpha(1A)-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca(2+) channel blocker), 5-methylurapidil (alpha(1A)-adrenoceptor antagonist), chloroethylclonidine (alpha(1B)-adrenoceptor antagonist) and BMY 7378 (alpha(1D)-adrenoceptor antagonist).


RESULTS
In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses.


CONCLUSIONS
The data demonstrated that there was a functional coexistence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic alpha-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR.
Khan
Md Abdul Hye
MA
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia. ahkhan@tulane.edu
Sattar
Munavvar Abdul
MA
Abdullah
Nor Azizan
NA
Abdulla
Mohammed H
MH
Salman
Ibrahim M
IM
Kazi
Raisa N
RN
Swarup
K R L Anand
KR
Rathore
Hassaan A
HA
Basri
Fathihah
F
Hussain
Nurjannah M
NM
Dewa
Aidiahmad
A
Johns
Edward James
EJ
D018674:Adrenergic Antagonists / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000378:metabolism*; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D018674:Adrenergic Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D017311:Amlodipine; D010656:Phenylephrine; D013311:Streptozocin; D008729:Methoxamine; D009638:Norepinephrine