Page last updated: 2024-10-24

negative regulation of glomerular filtration

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of glomerular filtration. Glomerular filtration is the processs whereby blood is filtered by the glomerulus into the renal tubule. [GOC:mtg_cardio]

Negative regulation of glomerular filtration is a complex physiological process that involves several mechanisms to control the rate at which blood is filtered by the kidneys. This filtration process, known as glomerular filtration, occurs in the glomerulus, a network of tiny blood vessels within the kidney. Here is a detailed description of the biological processes involved in negative regulation of glomerular filtration:

**1. Tubuloglomerular Feedback (TGF):**
* This mechanism involves the juxtaglomerular apparatus (JGA), a specialized structure located at the point where the distal convoluted tubule contacts the glomerulus.
* When the flow of filtrate in the distal tubule increases (e.g., due to high blood pressure or high sodium levels), the JGA senses this increase.
* The JGA then releases vasoconstrictor substances, primarily adenosine and ATP, which act on the afferent arteriole, the blood vessel supplying the glomerulus.
* This constriction reduces blood flow into the glomerulus, thereby decreasing glomerular filtration rate (GFR).

**2. Sympathetic Nervous System:**
* The sympathetic nervous system can regulate GFR through the release of norepinephrine.
* When activated, norepinephrine constricts the afferent arterioles, reducing blood flow into the glomerulus and decreasing GFR.
* This response is important for maintaining blood pressure during stress or exercise.

**3. Renin-Angiotensin-Aldosterone System (RAAS):**
* The RAAS is a complex hormonal system that plays a major role in regulating blood volume and blood pressure.
* When blood pressure drops, the juxtaglomerular cells of the JGA release renin.
* Renin initiates a cascade that ultimately leads to the production of angiotensin II, a potent vasoconstrictor.
* Angiotensin II constricts both the afferent and efferent arterioles, but its effect on the efferent arteriole is greater.
* This constriction reduces blood flow into the glomerulus and increases hydrostatic pressure in the glomerular capillaries, which further decreases GFR.

**4. Hormonal Regulation:**
* Other hormones, such as atrial natriuretic peptide (ANP), can also regulate GFR.
* ANP is released from the heart in response to high blood pressure or high blood volume.
* It acts to dilate afferent arterioles and constrict efferent arterioles, increasing GFR and promoting fluid excretion.

**5. Autoregulation:**
* The kidneys have an intrinsic ability to maintain a stable GFR over a wide range of blood pressures, known as autoregulation.
* This mechanism involves the smooth muscle cells in the afferent arterioles, which can sense changes in blood pressure.
* When blood pressure drops, the smooth muscle cells relax, dilating the afferent arterioles to increase blood flow into the glomerulus and maintain GFR. Conversely, when blood pressure increases, the smooth muscle cells contract, constricting the arterioles and reducing GFR.

**Overall, negative regulation of glomerular filtration is a coordinated effort by multiple mechanisms to maintain a stable GFR and ensure that the kidneys filter blood at an appropriate rate. These mechanisms work together to prevent excessive fluid loss and to maintain blood pressure within a normal range.**'
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Proteins (1)

ProteinDefinitionTaxonomy
Proteinase-activated receptor 1A proteinase-activated receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P25116]Homo sapiens (human)

Compounds (15)

CompoundDefinitionClassesRoles
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first sourcechromones;
morpholines;
organochlorine compound
autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
ultram2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol : A tertiary alcohol that is cyclohexanol substituted at positions 1 and 2 by 3-methoxyphenyl and dimethylaminomethyl groups respectively.aromatic ether;
tertiary alcohol;
tertiary amino compound
omega-n-methylarginineN(omega)-methyl-L-arginine : A L-arginine derivative with a N(omega)-methyl substituent.

omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.
amino acid zwitterion;
arginine derivative;
guanidines;
L-arginine derivative;
non-proteinogenic L-alpha-amino acid
vu0099704VU0099704: an antagonist of protease activated receptor 4 (PAR-4); structure in first source
2-bromo-N-[3-(1-oxopropylamino)phenyl]benzamidebenzamides
2-bromo-N-[3-(1-oxobutylamino)phenyl]benzamidebenzamides
sch 79797quinazolines
morphineMeconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound
anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
tapentadolTapentadol: An opioid analgesic, MU OPIOID RECEPTOR agonist, and noradrenaline reuptake inhibitor that is used in the treatment of moderate to severe pain, and of pain associated with DIABETIC NEUROPATHIES.alkylbenzene
o-demethyltramadolalkylbenzene;
ring assembly
rwj-56110RWJ-56110: a PAR-1 antagonist; structure in first source
vorapaxarvorapaxar : A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation.

vorapaxar: has antiplatelet activity; structure in first source
carbamate ester;
lactone;
naphthofuran;
organofluorine compound;
pyridines
cardiovascular drug;
platelet aggregation inhibitor;
protease-activated receptor-1 antagonist
e 5555E 5555: a 2-iminopyridine derivative and platelet aggregation inhibitoraromatic ketone
zstk474ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase.benzimidazoles;
morpholines;
organofluorine compound;
triamino-1,3,5-triazine
antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
AZ3451benzimidazoles;
benzodioxoles;
nitrile;
organobromine compound;
secondary carboxamide
anti-inflammatory agent;
autophagy inducer;
PAR2 negative allosteric modulator